A phase Ib trial study of trabectedin when prescribed in combination with durvalumab in locally advanced/unresectable soft-tissue sarcoma and ovarian carcinomas.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
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.
Institut Bergonié
Bordeaux, France
Centre Léon Bérard
Lyon, France
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)
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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
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
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
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
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
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
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
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
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