Ovarian Carcinoma, Soft Tissue Sarcoma
Conditions
Keywords
Advanced tumor, Pretreated tumor, Soft Tissue Sarcomas, Ovarian Carcinomas, Phase Ib, Circulating DNA
Brief summary
A phase Ib trial study of trabectedin when prescribed in combination with durvalumab in locally advanced/unresectable soft-tissue sarcoma and ovarian carcinomas.
Detailed description
This is a multicenter, prospective phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Trabectedin given with durvalumab, followed by two expansion cohorts once the MTD is established.
Interventions
DRUGCombination of trabectedin with durvalumab
Dose Escalation : 3 doses of trabectedin given in combination with durvalumab (fixed dose) will be investigated. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Expansion cohorts: Once the Maximum Tolerated Dose (MTD) has been defined, the expansion cohorts will be opened. All patients will be treated at the MTD of Trabectedin (as defined in the dose escalation part of the trial) given in association with Durvalumab with the same schedule as in the dose escalation part of the trial.
Sponsors
AstraZeneca
PharmaMar
Institut Bergonié
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of trabectedin when prescribed in combination with durvalumab followed by two expansion cohorts (Soft-tissue sarcomas and ovarian carcinomas) once the MTD is established
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histology : * Soft-tissue sarcoma histologically confirmed. In care outside a center of the RRePS Network, a central review is necessary (Pr. Coindre team), * histologically confirmed ovarian carcinoma (carcinosarcoma included), or ovarian carcinoma without known g/s BRCA mutation 2. Ovarian carcinoma must have received at least one line of platinum-containing regimen 3. Metastatic or unresectable locally advanced disease, not amenable to curative therapy 4. Age ≥ 18 years, 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1, 6. Life expectancy \> 3 months, 7. Patients must have measurable disease (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST 1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as \> 10 mm with spiral CT scan. 8. Documented disease progression according to RECIST v1.1 before study entry, 9. Patient must comply with the collection of tumor biopsies, 10. At least 1 line of chemotherapy in the palliative setting with use of Anthracyclines (for STS), 11. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy, 12. Adequate hematological, renal, metabolic and hepatic function: 1. Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 x 109/l, and platelet count ≥ 100 x 109/l. 2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 in case of extensive liver involvement) and alkaline phosphatase (AP) ≤ 2.5 x ULN. 3. Total bilirubin ≤ ULN. 4. Albumin ≥ 25 g/l. 5. Calculated creatinine clearance (CrCl) \> 60 ml/min (according to Cockroft Gault formula). 6. Thyroid function within normal laboratory ranges (TSH, free T3, free T4). 7. Creatine Phosphokinase (CPK) ≤ 2.5 x ULN 13. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for six months after discontinuation of treatment. 14. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma, 15. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.0), 16. Voluntarily signed and dated written informed consent prior to any study specific procedure, 17. Patients with a social security in compliance with the French law .
Exclusion criteria
1. Previous treatment with Trabectedin or an anti-PD-1, anti-PD-L1, anti-PD-L2, including durvalumab 2. Current or prior use of immunosuppressive medication medication including any use of oral glucocorticoids, within 21 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses 3. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), 4. Has an active autoimmune disease requiring systemic treatment within the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insuddiciency) is not considered a form of systemic treatment, 5. Has evidence of active non-infectious pneumonitis, 6. Has an active infection requiring systemic therapy, 7. Currently active bacterial or fungus infection (\> grade 2 CTC \[CTCAE\] HIV1, HIV2, hepatitis A or hepatitis B or hepatitis C infections, 8. Known central nervous system malignancy (CNS), 9. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding, 10. Previous enrolment in the present study, 11. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons, 12. Has received a live vaccine within 30 days prior to the first dose of trial treatment. Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. 13. Known hypersensitivity to any involved study drug or any of its formulation components, 14. Tumors not accessible for biopsy, 15. Known history of active tuberculosis 16. Person under judicial protection or deprived of liberty, 17. Cardiac dysfunction: LVEF \< 40% at Baseline or clinically symptomatic cardiac dysfunction (any % of LVEF at Baseline) 18. Concomitant use of strong inhibitor or inductors of cytochrome CYP3A4 taken within 21 days prior to the first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Part: Establish the Recommended Phase II Dose (RP2D), the Maximum Tolerated Dose (MTD) Evaluated on the First Cycle (D1 to D21), the Safety Profile, and the Dose Limiting Toxicities (DLT) of Trabectedin Given in Combination With Durvalumab | During the first cycle (21 days) | A DLT is defined as an AE or laboratory abnormality that fulfills all the criteria below: * Begins on the first 21 days of treatment. * Is considered to be at least possibly related to the study treatment. * Meets one of the criteria below, graded as outlined or according to NCI-CTCAEv4.03 : * Any grade-4 toxicity (except for vomiting without maximal symptomatic/prophylactic treatment and if toxicity is transaminitis, but which have to be resolved at Day 21, i.e. return to Baseline or grade 1). * Grade-3 non-haematological toxicity lasting \> 7days. * Grade-3 hematologic toxicity lasting for \> 7days. * Grade 4 neutropenia with fever. * Grade \> 2 thrombocytopenia with bleeding. Endpoints: * Toxicity graded using the common toxicity criteria from the the NCI-CTCAE v4.03. * Incidence rate of DLT at each dose level during the first 21 days. |
| Expansion Cohorts : Evaluate Preliminary Signs of the Antitumor Activity of Trabectedin Given in Combination With Durvalumab in Terms of Objective Response Under Treatment. | Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months | Following RECIST v1.1 recommendations: * Objective response rate (ORR) is defined as the proportion of patients with complete or partial response (CR, PR) as per RECIST v1.1 criteria. * Objective response under treatment is recorded from study treatment initiation until the end of treatment and determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. * Disease status under treatment, whatever the response observed, will be centrally reviewed for all patients, by an independent expert radiologist. Reviewed data will be used for the efficacy analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Part : Progression-free Rate (PFR) at 6-month | 6-month progression-free Rate (PFR) as per RECIST v1.1 | Progression-free rate (PFR) is defined as the proportion of patients with complete response, partial response or stable disease more than 24 weeks as defined as per RECIST v1.1 criteria. 6-month PFR will be reported. Following RECIST v1.1 recommendations, claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
| Dose Escalation Part : 1-year Progression-free Survival (PFS) | 1-year progression-free survival (PFS) rate as per RECIST v1.1 | Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first. 1-year PFS rate will be reported. |
| Dose Escalation Part : 1-year Overall Survival (OS) | 1-year Overall Survival (OS) as per RECIST v1.1 | Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause). 1-year OS rate will be reported. |
| Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months | Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria: Following RECIST v1.1 recommendations: The best overall response is determined once all the data for the patient is known. Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
| Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months | Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria: Following RECIST v1.1 recommendations: * The best overall response is determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
| Expansion Cohorts: 6-month Progression-free Rate (PFR) | 6-month progression-free rate (PFR) as per RECIST v1.1 | Progression-free rate (PFR) is defined as the proportion of patients with complete response, partial response or stable disease more than 24 weeks as defined as per RECIST v1.1 criteria. 6-month PFR will be reported. . Following RECIST v1.1 recommendations, claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
| Expansion Cohorts: 1-year Progression-free Survival (PFS) | 1-year Progression-free survival (PFS) as per RECIST v1.1 | Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first. 1-year PFS rate will be reported. |
| Expansion Cohort : 1-year Overall Survival (OS) | 1-year Overall Survival (OS) as per RECIST v1.1 | Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause). 1-year OS rate will be reported. |
| Expansion Cohorts : 6-month Objective Response Rate (ORR) | 6-month Objective response rate (ORR) as per RECIST v1.1 | Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response according to RECIST v1.1 criteria. 6-month ORR will be reported. Following RECIST v1.1 recommendations: Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
| Dose Escalation Part : Objective Response Rate (ORR) | Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, an average of 5.1 months and ORR at 6-month | Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response according to RECIST v1.1 criteria. ORR under treatment and 6-month ORR will be reported ORR under treatment is recorded from study treatment initiation until the end of treatment. Following RECIST v1.1 recommendations: * ORR under treatment is determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. |
Countries
France
Participant flow
Recruitment details
40 patients were included of the study from October 19th 2017 to November 6th 2019. Inclusions were carried out in two French centers : Institut Bergonié, Bordeaux and Centre Léon Bérard, Lyon
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.
Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks. | 3 |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.
Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks. | 6 |
| Expansion Cohort - Soft-tissue Sarcoma (STS) Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.
Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks. | 16 |
| Expansion Cohort - Ovarian Carcinomas (OV) Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.
Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks. | 15 |
| Total | 40 |
Baseline characteristics
| Characteristic | Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohort - Soft-tissue Sarcoma (STS) | Expansion Cohort - Ovarian Carcinomas (OV) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 8 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 8 Participants | 9 Participants | 25 Participants |
| Age, Continuous | 52.6 years STANDARD_DEVIATION 7.7 | 58.1 years STANDARD_DEVIATION 7.6 | 53.5 years STANDARD_DEVIATION 18.1 | 64.2 years STANDARD_DEVIATION 6.6 | 58.1 years STANDARD_DEVIATION 13.3 |
| ECOG ECOG=0 | 2 Participants | 5 Participants | 10 Participants | 10 Participants | 27 Participants |
| ECOG ECOG=1 | 1 Participants | 1 Participants | 6 Participants | 5 Participants | 13 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 10 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 3 / 6 | 8 / 16 | 9 / 14 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 16 / 16 | 14 / 14 |
| serious Total, serious adverse events | 0 / 3 | 3 / 6 | 9 / 16 | 7 / 14 |
Outcome results
Primary
Dose Escalation Part: Establish the Recommended Phase II Dose (RP2D), the Maximum Tolerated Dose (MTD) Evaluated on the First Cycle (D1 to D21), the Safety Profile, and the Dose Limiting Toxicities (DLT) of Trabectedin Given in Combination With Durvalumab
A DLT is defined as an AE or laboratory abnormality that fulfills all the criteria below: * Begins on the first 21 days of treatment. * Is considered to be at least possibly related to the study treatment. * Meets one of the criteria below, graded as outlined or according to NCI-CTCAEv4.03 : * Any grade-4 toxicity (except for vomiting without maximal symptomatic/prophylactic treatment and if toxicity is transaminitis, but which have to be resolved at Day 21, i.e. return to Baseline or grade 1). * Grade-3 non-haematological toxicity lasting \> 7days. * Grade-3 hematologic toxicity lasting for \> 7days. * Grade 4 neutropenia with fever. * Grade \> 2 thrombocytopenia with bleeding. Endpoints: * Toxicity graded using the common toxicity criteria from the the NCI-CTCAE v4.03. * Incidence rate of DLT at each dose level during the first 21 days.
Time frame: During the first cycle (21 days)
Population: The following patients will not be included in the population assessable for safety (primary analysis) and thus will be replaced:~* Patients who received ≤ 75% RDI (Relative Dose Intensity) for trabectedin OR ≤ 75% RDI for durvalumab over cycle 1, due to drug-related AE not considered as DLT.~* Patients who goes off treatment over cycle 1 for reasons unrelated to toxicity (DLT or any other AE), e.g. progression, lost to follow-up, will be replaced
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part: Establish the Recommended Phase II Dose (RP2D), the Maximum Tolerated Dose (MTD) Evaluated on the First Cycle (D1 to D21), the Safety Profile, and the Dose Limiting Toxicities (DLT) of Trabectedin Given in Combination With Durvalumab | 0 Number of DLTs |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part: Establish the Recommended Phase II Dose (RP2D), the Maximum Tolerated Dose (MTD) Evaluated on the First Cycle (D1 to D21), the Safety Profile, and the Dose Limiting Toxicities (DLT) of Trabectedin Given in Combination With Durvalumab | 1 Number of DLTs |
Primary
Expansion Cohorts : Evaluate Preliminary Signs of the Antitumor Activity of Trabectedin Given in Combination With Durvalumab in Terms of Objective Response Under Treatment.
Following RECIST v1.1 recommendations: * Objective response rate (ORR) is defined as the proportion of patients with complete or partial response (CR, PR) as per RECIST v1.1 criteria. * Objective response under treatment is recorded from study treatment initiation until the end of treatment and determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors. * Disease status under treatment, whatever the response observed, will be centrally reviewed for all patients, by an independent expert radiologist. Reviewed data will be used for the efficacy analysis.
Time frame: Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months
Population: Population assessable for efficacy: All patients eligible and for whom the following conditions are statisfied:~* Received at least one complete or two incomplete treatment cycles,~* At least one disease measurement recorded not less than six weeks after treatment onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts : Evaluate Preliminary Signs of the Antitumor Activity of Trabectedin Given in Combination With Durvalumab in Terms of Objective Response Under Treatment. | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts : Evaluate Preliminary Signs of the Antitumor Activity of Trabectedin Given in Combination With Durvalumab in Terms of Objective Response Under Treatment. | 3 Participants |
Secondary
Dose Escalation Part : 1-year Overall Survival (OS)
Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause). 1-year OS rate will be reported.
Time frame: 1-year Overall Survival (OS) as per RECIST v1.1
Population: Given the small sample size in each arm (3 patients in the arm Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) and 6 patients in the arm Dose Escalation (Trabectedin Dose Level 1,2 mg/m²), we had pre-specified to combine these 2 arms, regardless of dose administered, for the calculation of Dose Escalation Part : 1-year Overall Survival (OS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part : 1-year Overall Survival (OS) | 88.9 percentage of participants |
Secondary
Dose Escalation Part : 1-year Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first. 1-year PFS rate will be reported.
Time frame: 1-year progression-free survival (PFS) rate as per RECIST v1.1
Population: Given the small sample size in each arm (3 patients in the arm Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) and 6 patients in the arm Dose Escalation (Trabectedin Dose Level 1,2 mg/m²), we had pre-specified to combine these 2 arms, regardless of dose administered, for the calculation of Dose Escalation Part : 1-year Progression-free Survival (PFS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part : 1-year Progression-free Survival (PFS) | 22.2 percentage of participants |
Secondary
Dose Escalation Part : Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response according to RECIST v1.1 criteria. ORR under treatment and 6-month ORR will be reported ORR under treatment is recorded from study treatment initiation until the end of treatment. Following RECIST v1.1 recommendations: * ORR under treatment is determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, an average of 5.1 months and ORR at 6-month
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part : Objective Response Rate (ORR) | 6-month Objective response | 0 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part : Objective Response Rate (ORR) | Objective response under treatment | 0 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part : Objective Response Rate (ORR) | 6-month Objective response | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part : Objective Response Rate (ORR) | Objective response under treatment | 1 Participants |
Secondary
Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR)
Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria: Following RECIST v1.1 recommendations: * The best overall response is determined once all the data for the patient is known. * Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Progressive disease | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Complete response | 0 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Stable disease | 2 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Complete response | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Stable disease | 4 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Progressive disease | 1 Participants |
Secondary
Dose Escalation Part : Progression-free Rate (PFR) at 6-month
Progression-free rate (PFR) is defined as the proportion of patients with complete response, partial response or stable disease more than 24 weeks as defined as per RECIST v1.1 criteria. 6-month PFR will be reported. Following RECIST v1.1 recommendations, claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: 6-month progression-free Rate (PFR) as per RECIST v1.1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Dose Escalation Part : Progression-free Rate (PFR) at 6-month | 2 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Dose Escalation Part : Progression-free Rate (PFR) at 6-month | 3 Participants |
Secondary
Expansion Cohort : 1-year Overall Survival (OS)
Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause). 1-year OS rate will be reported.
Time frame: 1-year Overall Survival (OS) as per RECIST v1.1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohort : 1-year Overall Survival (OS) | 56.3 percentage of participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohort : 1-year Overall Survival (OS) | 57.1 percentage of participants |
Secondary
Expansion Cohorts: 1-year Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first. 1-year PFS rate will be reported.
Time frame: 1-year Progression-free survival (PFS) as per RECIST v1.1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: 1-year Progression-free Survival (PFS) | 14.3 percentage of participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: 1-year Progression-free Survival (PFS) | 7.1 percentage of participants |
Secondary
Expansion Cohorts : 6-month Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response according to RECIST v1.1 criteria. 6-month ORR will be reported. Following RECIST v1.1 recommendations: Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: 6-month Objective response rate (ORR) as per RECIST v1.1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts : 6-month Objective Response Rate (ORR) | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts : 6-month Objective Response Rate (ORR) | 3 Participants |
Secondary
Expansion Cohorts: 6-month Progression-free Rate (PFR)
Progression-free rate (PFR) is defined as the proportion of patients with complete response, partial response or stable disease more than 24 weeks as defined as per RECIST v1.1 criteria. 6-month PFR will be reported. . Following RECIST v1.1 recommendations, claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: 6-month progression-free rate (PFR) as per RECIST v1.1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: 6-month Progression-free Rate (PFR) | 4 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: 6-month Progression-free Rate (PFR) | 6 Participants |
Secondary
Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR)
Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria: Following RECIST v1.1 recommendations: The best overall response is determined once all the data for the patient is known. Claimed responses will have to be confirmed at least 4 weeks later to ensure responses identified are not the result of measurement errors.
Time frame: Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 5.1 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Partial response | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Stable disease | 8 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Progressive disease | 4 Participants |
| Dose Escalation (Trabectedin Dose Level 1,0 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Not evaluable | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Not evaluable | 1 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Partial response | 3 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Progressive disease | 5 Participants |
| Dose Escalation (Trabectedin Dose Level 1,2 mg/m²) | Expansion Cohorts: Preliminary Signs of Antitumor Activity, Best Overall Response (BOR) | Stable disease | 5 Participants |