Stage A1 and B: Oesophageal carcinoma Stage A2: Any advanced solid tumours (carcinomas) MedDRA version: 20.0 Level: PT Classification code 10030137 Term: Oesophageal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: M6620
Product Code: M6620
Pharmaceutical Form: Solution for infusion
Current Sponsor code: M6620
Other descriptive name: M
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Any gender, age 16 years or over 2. Life expectancy of at least 12 weeks (N/A Stage B) 3. ECOG performance score of 0-1 4. 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 5. Able to give written (signed and dated) informed consent according to GCP before registration 6. Haematological and biochemical indices: Platelet count = 100 x 10^9/L; Absolute neutrophil count (ANC) = 1.5 x 10^9/L; Total bilirubin = 1.5 x upper limit of normal unless the subject has known or suspected Gilbert’s syndrome; AST (SGOT)/ALT (SGPT) = 2.5 x upper limit of normal; =5 X ULN if liver metastases Additional for Stage A1 1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus(not including cervical oesophagous) 2. Tumour length 10 cm 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 (up to 42 days before first study dose) and endoscopy 5. No oesophageal stent in situ 6. Haemoglobin (Hb) = 8.0 g/dL 7. Estimated glomerular filtration rate =40mL/min 8. Previous chemotherapy treatment completed 28 days before first study dose Additional for Stage A2 1. Any histologically confirmed advanced solid tumour that is metastatic or unresectable where investigator considers Cisplatin and Capecitabine based regimen as appropriate 2. Baseline investigations available: staging CT scan (up to 35 days before first study dose) 3. Haemoglobin (Hb) = 10.0 g/dL 4. Estimated glomerular filtration rate =60mL/min 5. Previous chemotherapy treatment completed 28 days before first study dose 6. Calcium, magnesium and phosphate within normal limits Additional for Stage B 1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus including Siewert type 1 or 2 tumours with =2cm gastric mucosal extension (not including cervical oesophagous). 2. Tumour 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 measureable disease. 6. Diagnostic PET CT scan* 7. Staging CT scan* *either CT or PET CT within 42 days of first study dose 8. Adequate respiratory and cardiac function tests for safe delivery of CRT in the opinion of the Principal 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. Haemoglobin (Hb) 10.0 g/dL 10. Estimated glomerular filtration rate =60mL/min 11. Calcium, magnesium and phosphate within normal limi
Exclusion criteria
Exclusion criteria: A patient will not be eligible for the trial if any of the following apply: 1. Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used 2. 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 a 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 >450 msec in adult male and >470 msec in adult females (by either Fridericia’s or Bazett’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 enrolment 12. Strong CYP3A inhibitors and inducers or Haemopoetic growth factors within 14 days before first dose M6620 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 exclusion criteria Stage A1 and B 1. Previous radiotherapy to thorax or upper abdomen Additional exclusion criteria Stage A2 and B 1. History of hand-foot syndrome 2. History of hearing impairment 3. Live vaccine received within 30 days prior to treatment start Additional exclusion criteria Stage B 1. Previous chemotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Stage A1: 9 weeks from start of treatment Stage A2: 4 weeks from start of treatment Stage B: 24 weeks from start of treatment ; Main Objective: Stage A1: to find the best tolerated dose of the drug M6620 in combination with palliative radiotherapy in patients with oesophageal cancer. Stage A2: to find the best tolerated dose of the drug M6620 in combination with palliative cisplatin/capecitabine chemotherapy in patients with advanced solid tumours. Stage B: to find the best tolerated M6620 treatment schedule in combination with curative chemoradiotherapy in patients with oesophageal cancer. ; Secondary Objective: Stage A1: to determine the safety and toxicity profile of the drug M6620 when given with radiotherapy for palliative treatment of oesophageal cancer (treatment of symptoms and to slow the growth of the cancer) Stage A1: to determine if M6620 can be given in combination with radiotherapy without compromising the ability to give appropriate radiotherapy treatment. Stage A1: to determine the effectiveness of the combination of M6620 and radiotherapy treatment. Stage A2: To determine the safety and toxicity profile of the drug M6620 when given with chemotherapy (cisplatin and capecitabine) for palliative treatment of advanced solid tumours. Stage A2: to determine if M6620 can be given in combination with chemotherapy without compromising the ability to give appropriate chemotherapy treatment. Stage A2: to determine the effectiveness of the combination of M6620 and chemotherapy treatment. Stage B: to determine the safety and toxicity profile of the drug M6620 when given with chemoradioth ; Primary end point(s): Stage A1: Highest treatment schedule resulting in less than 25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Endpoints 1 to 3: All Stages: 1. Any toxicity grade =3 graded according to CTCAE v4.03 and length of time for toxicity to resolve 2. Objective tumour response (OR) as evaluated by CT scan and quantified by Response Criteria Evaluation (RECIST 1.1) and in Stage B endoscopic and biopsy findings 3. PFS and OS rates from D1 Endpoint 4: Stage A1 4. Proportion of patients completing at least 75%, 90% and 100% of the planned RT dose Stage A2 4. Proportion of patients completing at least 75%, 90% and 100% of the planned dose Stage B: 4. 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 ; Timepoint(s) of evaluation of this end point: Endpoint number from above: 1. Stage A1, A2 and B: 12 weeks; 26 weeks & 24 weeks respectively 2. Stage A1, A2 and B: 12 weeks; 26 weeks & 24 weeks respectively 3. Stage A1/2 and B: 6 and 12 months; 12 and 24 months respectively 4. Stage A1, A2 and B: 3 weeks; 18 weeks & 11 weeks respectively | — |
Countries
United Kingdom
Contacts
Public ContactCHARIOT Trial Manager
Oncology Clinical Trials Office, University of Oxford
Outcome results
None listed