Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.

NCT03085225 | Completed Phase 1 Results DMC

• 1 other identifier: IB2016-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Ovarian Carcinoma; Soft Tissue Sarcoma

Keywords

Advanced tumor; Pretreated tumor; Soft Tissue Sarcomas; Ovarian Carcinomas; Phase Ib; Circulating DNA

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

Secondary Outcomes (10)

• 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

• 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

• Dose Escalation Part : Progression-free Rate (PFR) at 6-month

  6-month progression-free Rate (PFR) as per RECIST v1.1

• Dose Escalation Part : 1-year Progression-free Survival (PFS)

  1-year progression-free survival (PFS) rate as per RECIST v1.1

• Dose Escalation Part : 1-year Overall Survival (OS)

  1-year Overall Survival (OS) as per RECIST v1.1

Study Arms (1)

Combination of trabectedin with durvalumab

EXPERIMENTAL

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.

Drug: Combination of trabectedin with durvalumab

Interventions

Combination of trabectedin with durvalumab DRUG

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.

Combination of trabectedin with durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Ovarian carcinoma must have received at least one line of platinum-containing regimen
• Metastatic or unresectable locally advanced disease, not amenable to curative therapy
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,
• Life expectancy \> 3 months,
• Documented disease progression according to RECIST v1.1 before study entry,
• Patient must comply with the collection of tumor biopsies,
• At least 1 line of chemotherapy in the palliative setting with use of Anthracyclines (for STS),
• At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
• Adequate hematological, renal, metabolic and hepatic function:
• 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.
• 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.

You may not qualify if:

• Previous treatment with Trabectedin or an anti-PD-1, anti-PD-L1, anti-PD-L2, including durvalumab
• 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
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis),
• 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,
• Has evidence of active non-infectious pneumonitis,
• Has an active infection requiring systemic therapy,
• Currently active bacterial or fungus infection (\> grade 2 CTC \[CTCAE\] HIV1, HIV2, hepatitis A or hepatitis B or hepatitis C infections,
• Known central nervous system malignancy (CNS),
• 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,
• Previous enrolment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
• 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.
• Known hypersensitivity to any involved study drug or any of its formulation components,
• Tumors not accessible for biopsy,

Sponsors & Collaborators

• Institut Bergonié: lead
• AstraZeneca: collaborator
• PharmaMar: collaborator

Study Sites (2)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Sarcoma

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Results Point of Contact

• Title: Pr Simone Mathoulin-Pelissier
• Organization: Institut Bergonié

S.Mathoulin@bordeaux.unicancer.fr

0556333333

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 21, 2017
• Study Start: May 5, 2017
• Primary Completion: November 19, 2020
• Study Completion: January 4, 2022
• Last Updated: September 4, 2025
• Results First Posted: September 4, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)