Oesophageal Adenocarcinoma, Solid Tumor, Squamous Cell Carcinoma
Conditions
Keywords
Oesophageal cancer
Brief summary
This Phase I study will test the combination of a novel ATR inhibitor (M6620) with chemoradiotherapy in oesophageal cancer; utilizing three experimental cohorts (Stage A1, A2 and B).
Detailed description
There is strong scientific rationale for combining ATR inhibitors with DNA damaging agents such as radiation and cisplatin. In particular, ATR inhibition has been shown to be cytotoxic to tumor cells with an impaired DNA damage response, such as those with deficiency in the ATM- or p53 pathway. The high incidence of p53 mutations and the fact that cisplatin and radiation are key therapeutics, makes oesophageal cancer an attractive tumor type to test the activity of an ATR inhibitor. Given the reported synthetic lethal relationship between ATM and ATR, it is likely that ATR inhibition in an ATM- or p53- deficient background will offer a specific and effective way of targeting OAC and SCC of the oesophagus, and enhance the current standard of care. The trial will be divided into three stages. Stage A1 will explore the combination of M6620 plus radiotherapy in the palliative setting and Stage A2 will explore the combination of M6620 plus chemotherapy in the palliative setting. Stage B, will explore the combination of all 3 (M6620 plus chemoradiotherapy in the radical setting). In Stage A1 of the study M6620 will be combined with radiotherapy for the first time and the starting dose will be 140mg/m2 M6620, which has been well-tolerated. M6620 will be administered with daily palliative radiotherapy during this stage in order to study the specific interaction of M6620 with radiotherapy (acting as the DNA damaging agent during this trial stage). In Stage A2 of the study, M6620 will be combined with Cisplatin and Capecitabine combination chemotherapy for the first time; with a starting dose of 90mg/m2 M6620. M6620 will be administered 24 hours post cisplatin infusion, aiming to achieve maximum treatment benefit. Stage A1 and A2 together will help give an indication of a toxicity profile before administration with chemoradiotherapy (Stage B).
Interventions
DRUGM6620
M6620 is an unlicensed small molecule ATR inhibitor which can be used in combination with DNA damaging agents. In pre-clinical models it has substantial activity when given with DNA damaging drugs or ionising radiation. The clinical agent (M6620) is currently studied in a phase I trial in Oxford and other centres in combination with gemcitabine, cisplatin, gemcitabine/cisplatin and cisplatin/etoposide.
DRUGCisplatin
Cisplatin is a platinum based chemotherapy drug licensed to treat a number of different types of cancer. Cisplatin use is not considered standard practice in Stage A2 & B, therefore Cisplatin is considered an investigational medicinal product for the purpose of this trial.
DRUGCapecitabine
Capecitabine is a chemotherapy drug licensed to treat a number of different types of cancer, it is a noncytotoxic pre-cursor of the cytotoxic 5-fluourouracil. Capecitabine use is not considered standard practice in Stage A2 & B, therefore Capecitabine is considered an investigational medicinal product for the purpose of this trial.
RADIATIONRadiotherapy
Stage A1 uses palliative radiotherapy. Stage B uses definitive radiotherapy.
Sponsors
Merck KGaA, Darmstadt, Germany
University of Oxford
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
CHARIOT will use a single arm, open-label, dose escalation, Time-To-Event Continual Reassessment Method (TiTE-CRM) to find the optimal treatment schedule.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Stage A1: 1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus (not including cervical oesophagus) 2. Tumor length 15cm or less 3. Any stage of disease that is unsuitable for radical CRT or surgery but suitable for palliative RT 4. Baseline investigations available: staging CT scan (within 42 days before first study dose) and endoscopy 5. Previous chemotherapy treatment completed 28 days before first study dose 6. No oesophageal stent in-situ 7. Any gender, aged ≥16 years. 8. Life expectancy of at least 12 weeks 9. ECOG performance score of 0-1 10. Able to comply with protocol fully - absence of any physical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 11. Able to give written (signed and dated) informed consent according to GCP before registration 12. Hematological and biochemical indices within the ranges below: * Haemoglobin: ≥8.0g/dL * Platelet count : ≥100x10\^9/L * Absolute neutrophil count: ≥1.5x10\^9/L * Total bilirubin: ≤1.5 x upper limit of normal unless the subject has known or suspected Gilbert's syndrome * AST/ALT: ≤2.5 times the upper limit of normal; ≤5 times if liver metastases * Estimated glomerular filtration rate: ≥40ml/min For Stage A2: 1. Any histologically confirmed advanced solid tumor that is metastatic or unresectable where Investigator considers Cisplatin and Capecitabine based regimen as appropriate. 2. Baseline investigations available: staging CT scan (within 35 days before first study dose) 3. Previous chemotherapy treatment completed 28 days before first study dose 4. Any gender, aged ≥16 years 5. Life expectancy of at least 12 weeks 6. ECOG performance score of 0-1 7. Able to comply with protocol fully - absence of any physical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 8. Able to give written (signed and dated) informed consent according to GCP before registration 9. Hematological and biochemical indices within the ranges below: * Haemoglobin: ≥10.0g/dL * Platelet count : ≥100x10\^9/L * Absolute neutrophil count: ≥1.5x10\^9/L * Total bilirubin: ≤1.5 x upper limit of normal unless the subject has known or suspected Gilbert's syndrome * AST/ALT: ≤2.5 times the upper limit of normal; ≤5 times if liver metastases * Ca, Mg, Phosphate: within normal limits * Estimated glomerular filtration rate: ≥60ml/min For Stage B: 1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus including Siewert type 1 or 2 tumors with ≤2cm gastric mucosal extension (not including cervical oesophagus) 2. Tumor length 7cm or less 3. Suitable for radical CRT and surgery not an option due to being medically unfit or unsuitable for surgery or patient choice 4. No oesophageal stent in-situ 5. Endoscopically or radiologically documented measurable disease 6. Diagnostic PET CT scan\* 7. Staging CT scan\* \*either CT or PET CT scan within 42 days of first study dose 8. Adequate respiratory and cardiac function tests for safe delivery of CRT in the opinion of the Principle Investigator, specifically cardiac ejection fraction ≥60% and lung function FEV1\>1 litre or 40% of predicted value or KCO (DLCO/VA) \>40% predicted value. 9. Any gender, aged ≥16 years 10. ECOG performance score of 0-1 11. Able to comply with protocol fully - absence of any physical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 12. Able to give written (signed and dated) informed consent according to GCP before registration 13. Haematological and biochemical indices within the ranges below: * Haemoglobin: ≥10.0g/dL * Platelet count : ≥100x10\^9/L * Absolute neutrophil count: ≥1.5x10\^9/L * Total bilirubin: ≤1.5 x upper limit of normal unless the subject has known or suspected Gilbert's syndrome * AST/ALT: ≤2.5 times the upper limit of normal; ≤5 times if liver metastases * Ca, Mg, Phosphate: within normal limits * Estimated glomerular filtration rate: ≥60ml/min
Exclusion criteria
1. Pregnant or breast-feeding women, or women of childbearing potential unless highly effective contraception is used 2. Untreated and multiple brain metastases 3. Clinically significant cardiovascular event within 6 months before study entry to include: a) congestive heart failure requiring therapy, b) unstable angina pectoris, c) myocardial infarction, d) class II/III/IV cardiac disease (New York Heart Association), e) presence of severe valvular heart disease, f) presence of ventricular arrhythmia requiring treatment 4. History of arrhythmia that is symptomatic or requires treatment (CTCAE 3), symptomatic or uncontrolled atrial fibrillation, despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted. 5. Uncontrolled hypertension (blood pressure ≥160/100 despite optimal therapy) 6. Second or third degree heart block with or without symptoms 7. QTc \>450msec in adult male and \>470 msec in adult females (by Fridericia's correction) not due to electrolyte abnormality and that does not resolve with correction of electrolytes. 8. History of congenital long QT syndrome 9. History of torsades de pointes (or any concurrent medication with a known risk of inducing torsades de pointes) 10. Trachea-oesophageal fistula or invasion of the tracheo-bronchial tree 11. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to the start of treatment 12. Strong CYP3A inhibitors and inducers or haemopoietic growth factors within 14 days before first dose of M6620 (Berzosertib) 13. HER2 gastro-oesophageal positive cancer where anti-Her2 therapies may be more appropriate (however patients who have failed anti-HER2 therapy may be eligible for stage A1 and A2) 14. Unable to have or unwilling to change to low molecular weight heparin instead of Warfarin 15. Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results. 16. Any other active malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions. 17. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | From start of M6620 (Berzosertib) treatment to 6-week follow up visit (9 weeks) | To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with radiotherapy (RT) only in the palliative treatment of oesophageal cancer. |
| STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | From start of M6620 (Berzosertib) treatment to end of first week of cycle two of chemotherapy (4 weeks) | To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with chemotherapy (cisplatin and capecitabine) only in the palliative treatment of solid cancer. |
| STAGE B - To Determine the Best Tolerated M6620 (Berzosertib) Treatment Schedule (or RPTD) Administered Concomitantly With Radiotherapy (dCRT) in Combination With Cisplatin and Capecitabine in the Radical Treatment of Oesophageal Cancer. | 24 weeks | Highest treatment schedule resulting in less than 45% dose limiting toxicity (DLT) rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | From start of M6620 (Berzosertib) treatment to 8-week post-end of treatment follow up visit (26 weeks) | Toxicity profile when M6620 is administered concomitantly with chemotherapy in the treatment of oesophageal cancer. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death). |
| STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | From start of M6620 (Berzosertib) treatment to last dose (18 weeks) | Treatment compliance of M6620 (Berzosertib), capecitabine and cisplatin when taken concomitantly. |
| STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | At 12 weeks following start of M6620 (Berzosertib) treatment | Efficacy of the combination (M6620 and chemotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026). From Progressive Disease (PD) to Complete Response (CR). |
| STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | From start of M6620 (Berzosertib) treatment to 9-week follow up visit (12 weeks) | Toxicity profile when M6620 is administered concomitantly with RT in the palliative treatment of oesophageal cancer. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death). |
| STAGE B - To Determine Tolerance and Ability to Deliver M6620 (Berzosertib) in Combination With Standard dCRT. | 24 weeks | Treatment tolerance and deliverability measured by proportion of patients completing at least 80% of the planned chemotherapy dose and at least 20 fractions of RT. |
| STAGE B - To Determine the Efficacy of the Long Term Safety of the Treatment Combination. | 24 weeks | To measure objective tumour response as evaluated by CT scan and quantified by RECIST 1.1 and endoscopic biopsy findings & PFS and OS from D1 |
| STAGE B - To Determine the Safety and Toxicity Profile of M6620 (Berzosertib) Administered Concomitantly With dCRT in Combination With Cisplatin and Capecitabine in the Radical Treatment of Oesophageal Cancer. | 24 weeks | Any toxicity grade ≥3 graded according to CTCAE v4.03 and length of time for toxicity to resolve. |
| STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | From start of M6620 (Berzosertib) treatment to last dose (3 weeks) | Treatment compliance of M6620 (Berzosertib) and palliative radiotherapy when taken concomitantly. |
| STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | At 12 weeks following start of M6620 (Berzosertib) treatment | Efficacy of the combination (M6620 and radiotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026). From Progressive Disease (PD) to Complete Response (CR). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A1 - Dose Level 1 Radiotherapy + M6620 (Berzosertib) administered at 140 mg/m2 on days 2, 9, 16. | 3 |
| A1 - Dose Level 2 Radiotherapy + M6620 (Berzosertib) administered at 140 mg/m2 on days 2, 5, 9, 12, 16. | 1 |
| A1 - Dose Level 3 Radiotherapy + M6620 (Berzosertib) administered at 140 mg/m2 on days 2, 5, 9, 12, 16, 19. | 1 |
| A1 - Dose Level 4 Radiotherapy + M6620 (Berzosertib) administered at 240 mg/m2 on days 2, 9, 16. | 1 |
| A1 - Dose Level 5 Radiotherapy + M6620 (Berzosertib) administered at 240 mg/m2 on days 2, 5, 9, 12, 16. | 1 |
| A1 - Dose Level 6 Radiotherapy + M6620 (Berzosertib) administered at 240 mg/m2 on days 2, 5, 9, 12, 16, 19. | 9 |
| A2 - Dose Level 1 Cisplatin/capecitabine + M6620 (Berzosertib) administered at 90 mg/m2 once a week for 18 weeks. | 5 |
| A2 - Dose Level 2 Cisplatin/capecitabine + M6620 (Berzosertib) administered at 90 mg/m2 twice a week for 18 weeks. | 1 |
| A2 - Dose Level 3 Cisplatin/capecitabine + M6620 (Berzosertib) administered at 140 mg/m2 once a week for 18 weeks. | 9 |
| A2 - Dose Level 4 Cisplatin/capecitabine + M6620 (Berzosertib) administered at 140 mg/m2 twice a week for 18 weeks. | 5 |
| Total | 36 |
Baseline characteristics
| Characteristic | A1 - Dose Level 2 | A1 - Dose Level 3 | A1 - Dose Level 4 | A1 - Dose Level 5 | A1 - Dose Level 6 | A1 - Dose Level 1 | A2 - Dose Level 1 | A2 - Dose Level 2 | A2 - Dose Level 3 | A2 - Dose Level 4 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 0 Participants | 6 Participants | 2 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 17 Participants |
| Distant Metastases No | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 11 Participants |
| Distant Metastases Yes | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 5 Participants | 1 Participants | 8 Participants | 5 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 9 Participants | 3 Participants | 5 Participants | 1 Participants | 9 Participants | 5 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Locoregional Disease No | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 13 Participants |
| Locoregional Disease Yes | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants | 1 Participants | 0 Participants | 6 Participants | 3 Participants | 23 Participants |
| Prior Radiotherapy No | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants | 3 Participants | 27 Participants |
| Prior Radiotherapy Yes | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 2 Participants | 2 Participants | 9 Participants |
| Prior Systemic Treatment No | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Prior Systemic Treatment Yes | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants | 2 Participants | 4 Participants | 1 Participants | 9 Participants | 5 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 6 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 8 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 23 Participants |
| Smoking status Current smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Smoking status Ex-smoker | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 20 Participants |
| Smoking status Never smoked | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants | 2 Participants | 15 Participants |
| Tumour grade Moderately differentiated (G2) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 8 Participants |
| Tumour grade Poorly differentiated (G3) | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 15 Participants |
| Tumour grade Unknown or cannot be assessed (GX) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 11 Participants |
| Tumour grade Well differentiated (G1) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 1 | 0 / 1 | 1 / 1 | 1 / 1 | 5 / 9 | 3 / 5 | 1 / 1 | 5 / 9 | 2 / 5 |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 9 / 9 | 4 / 5 | 1 / 1 | 9 / 9 | 4 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 2 / 9 | 0 / 5 | 0 / 1 | 3 / 9 | 0 / 5 |
Outcome results
Primary
STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer.
To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with radiotherapy (RT) only in the palliative treatment of oesophageal cancer.
Time frame: From start of M6620 (Berzosertib) treatment to 6-week follow up visit (9 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1 - Dose Level 1 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 2 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 3 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 4 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 5 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 6 | STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | 0 Dose Limiting Toxicities (DLTs) |
Comparison: The primary analysis is performed using the Time-To-Event Continual Reassessment Method (TiTE-CRM). Giving posterior estimates for the probability of toxicity (DLT) at each dose level.95% CI: [0, 0.165]
Primary
STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer.
To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with chemotherapy (cisplatin and capecitabine) only in the palliative treatment of solid cancer.
Time frame: From start of M6620 (Berzosertib) treatment to end of first week of cycle two of chemotherapy (4 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1 - Dose Level 1 | STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 2 | STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | 0 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 3 | STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | 2 Dose Limiting Toxicities (DLTs) |
| A1 - Dose Level 4 | STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | 0 Dose Limiting Toxicities (DLTs) |
Comparison: The primary analysis is performed using the Time-To-Event Continual Reassessment Method (TiTE CRM). Giving posterior estimates for the probability of toxicity (DLT) at each dose level.95% CI: [0.042, 0.397]
Primary
STAGE B - To Determine the Best Tolerated M6620 (Berzosertib) Treatment Schedule (or RPTD) Administered Concomitantly With Radiotherapy (dCRT) in Combination With Cisplatin and Capecitabine in the Radical Treatment of Oesophageal Cancer.
Highest treatment schedule resulting in less than 45% dose limiting toxicity (DLT) rate.
Time frame: 24 weeks
Population: Due to lack of funding, Stage B was not completed.
Secondary
STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy
Treatment compliance of M6620 (Berzosertib) and palliative radiotherapy when taken concomitantly.
Time frame: From start of M6620 (Berzosertib) treatment to last dose (3 weeks)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 3 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 1 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 2 Participants |
| A1 - Dose Level 1 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 1 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 1 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 1 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 1 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 1 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 1 Participants |
| A1 - Dose Level 4 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 1 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 1 Participants |
| A1 - Dose Level 5 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | <75% | 1 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=75%,<90% | 3 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | <75% | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=75%,<90% | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | >=90%, <100% | 2 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | Radiotherapy compliance | 100% | 7 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Palliative Radiotherapy | M6620 (Berzosertib) compliance | 100% | 5 Participants |
Secondary
STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1.
Efficacy of the combination (M6620 and radiotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026). From Progressive Disease (PD) to Complete Response (CR).
Time frame: At 12 weeks following start of M6620 (Berzosertib) treatment
Population: Overall RECIST at 12 Weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 1 Participants |
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 1 Participants |
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 1 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 1 Participants |
| A1 - Dose Level 2 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 1 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 1 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 1 Participants |
| A1 - Dose Level 5 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 2 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 2 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 1 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 3 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 1 Participants |
| A1 - Dose Level 6 | STAGE A1 - Objective Tumour Response to M6620 (Berzosertib) Plus Radiotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
Secondary
STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer.
Toxicity profile when M6620 is administered concomitantly with RT in the palliative treatment of oesophageal cancer. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death).
Time frame: From start of M6620 (Berzosertib) treatment to 9-week follow up visit (12 weeks)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1 - Dose Level 1 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 1 Participants |
| A1 - Dose Level 1 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 2 Participants |
| A1 - Dose Level 1 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 0 Participants |
| A1 - Dose Level 1 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 0 Participants |
| A1 - Dose Level 2 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 1 Participants |
| A1 - Dose Level 2 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 1 Participants |
| A1 - Dose Level 3 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 0 Participants |
| A1 - Dose Level 3 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 1 Participants |
| A1 - Dose Level 4 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 0 Participants |
| A1 - Dose Level 4 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 0 Participants |
| A1 - Dose Level 5 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 1 Participants |
| A1 - Dose Level 6 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 2 | 1 Participants |
| A1 - Dose Level 6 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 3 | 6 Participants |
| A1 - Dose Level 6 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 6 | STAGE A1 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer. | Worst AE: Grade 1 | 2 Participants |
Secondary
STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer.
Treatment compliance of M6620 (Berzosertib), capecitabine and cisplatin when taken concomitantly.
Time frame: From start of M6620 (Berzosertib) treatment to last dose (18 weeks)
Population: 2 participants were not included in this analysis as they did not take any IMP.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=75%, <90% | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | <75% | 3 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | 100% | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | 100% | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | 100% | 3 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | <75% | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | <75% | 3 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=90%, <100% | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=90%, <100% | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | 100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=75%, <90% | 1 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | <75% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=75%, <90% | 1 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=75%, <90% | 1 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | 100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | <75% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | <75% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | 100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | <75% | 8 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | 100% | 2 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=90%, <100% | 1 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | <75% | 6 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | 100% | 4 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=90%, <100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=75%, <90% | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | <75% | 5 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | 100% | 1 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | 100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | 100% | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | <75% | 4 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | <75% | 4 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | >=90%, <100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | <75% | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Capecitabine compliance | >=75%, <90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=75%, <90% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | M6620 (Berzosertib) compliance in cycle 1 | >=90%, <100% | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Number of Patients Completing at Least 75%, 90% and 100% of the Planned Treatment Dose of M6620 (Berzosertib) in Combination With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer. | Cisplatin compliance | 100% | 0 Participants |
Secondary
STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1.
Efficacy of the combination (M6620 and chemotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026). From Progressive Disease (PD) to Complete Response (CR).
Time frame: At 12 weeks following start of M6620 (Berzosertib) treatment
Population: Overall RECIST at 12 Weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 4 Participants |
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 1 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 2 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 6 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 1 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Missing Data | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Not Evaluable | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Partial Response | 1 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Stable Disease | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Complete Response | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Objective Tumour Response to M6620 (Berzosertib) Plus Chemotherapy, as Evaluated by CT Scan and Quantified by RECIST 1.1. | Progressive Disease | 0 Participants |
Secondary
STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer
Toxicity profile when M6620 is administered concomitantly with chemotherapy in the treatment of oesophageal cancer. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death).
Time frame: From start of M6620 (Berzosertib) treatment to 8-week post-end of treatment follow up visit (26 weeks)
Population: 2 participants were not included in this analysis as they did not take any IMP.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1 - Dose Level 1 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 3 | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 4 | 1 Participants |
| A1 - Dose Level 1 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 1 | 0 Participants |
| A1 - Dose Level 1 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 2 | 2 Participants |
| A1 - Dose Level 2 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 4 | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 2 | 1 Participants |
| A1 - Dose Level 2 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 1 | 0 Participants |
| A1 - Dose Level 2 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 3 | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 1 | 0 Participants |
| A1 - Dose Level 3 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 4 | 1 Participants |
| A1 - Dose Level 3 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 3 | 6 Participants |
| A1 - Dose Level 3 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 2 | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 4 | 1 Participants |
| A1 - Dose Level 4 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 3 | 2 Participants |
| A1 - Dose Level 4 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 1 | 0 Participants |
| A1 - Dose Level 4 | STAGE A2 - Severity of Worst Adverse Events for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer | Worst AE: Grade 2 | 1 Participants |
Secondary
STAGE B - To Determine the Efficacy of the Long Term Safety of the Treatment Combination.
To measure objective tumour response as evaluated by CT scan and quantified by RECIST 1.1 and endoscopic biopsy findings & PFS and OS from D1
Time frame: 24 weeks
Population: Due to lack of funding, Stage B was not completed.
Secondary
STAGE B - To Determine the Safety and Toxicity Profile of M6620 (Berzosertib) Administered Concomitantly With dCRT in Combination With Cisplatin and Capecitabine in the Radical Treatment of Oesophageal Cancer.
Any toxicity grade ≥3 graded according to CTCAE v4.03 and length of time for toxicity to resolve.
Time frame: 24 weeks
Population: Due to lack of funding, Stage B was not completed.
Secondary
STAGE B - To Determine Tolerance and Ability to Deliver M6620 (Berzosertib) in Combination With Standard dCRT.
Treatment tolerance and deliverability measured by proportion of patients completing at least 80% of the planned chemotherapy dose and at least 20 fractions of RT.
Time frame: 24 weeks
Population: Due to lack of funding, Stage B was not completed.