NCT03249142

Immunotherapy With Neo-adjuvant Chemotherapy for OVarian Cancer

A Multicentre Feasibility Randomized Study of Anti-PD-L1 Durvalumab (MEDI4736) With or Without Anti-CTLA-4 Tremelimumab in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma, Treated With a First-line Neo-adjuvant Strategy

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 69 (actual)
• Sponsor: ARCAGY/ GINECO GROUP · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, open, comparative, multi-centre study which will recruit up to 66 patients. The objective is mainly to explore the safety and feasibility in neo-adjuvant first-line ovarian cancer (including patients with primary peritoneal or fallopian tube adenocarcinoma) of various combinations of durvalumab with chemotherapy with or without tremelimumab.

Detailed description

The schedule is the following: • In a first step a run-in phase of 6 patients will be conducted to test the safety and feasibility of the combination of durvalumab with standard carboplatin-paclitaxel chemotherapy. Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab (day1) Cycle 3 : chemotherapy + durvalumab (day1) • In a second step, if first-step was found feasible, a run-in phase of 6 patients will be conducted to test the safety and feasibility of the combination of durvalumab plus tremelimumab with standard carboplatin-paclitaxel chemotherapy. Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab + tremelimumab (day1) Cycle 3 : chemotherapy + durvalumab (day1) * After the run-in phase, patients will be randomized in a ratio 1:1 between those included in the durvalumab-chemotherapy expansion phase (arm A) and those included in the durvalumab + tremelimumab-chemotherapy expansion phase (arm B). * This study will also allow to explore the feasibility of a salvage therapy personalized according to the results of interval surgery and type of previous neo-adjuvant therapy. 1. In those patients who achieved a complete surgical resection at interval debulking surgery, adjuvant treatment will include 3 cycles of durvalumab + chemotherapy and then a follow-up period. 2. In patients with residual tumor at interval debulking surgery, salvage therapy will depend on the initial treatment arm allocated. 1. In arm A, the tremelimumab will be added to the durvalumab-chemotherapy combination at day 1 of cycle 2 before a salvage surgery. Durvalumab (with one cycle of tremelimumab post S3) will be pursued in maintenance treatment, up to 1 year or until disease progression, unacceptable toxicity or patient withdrawn. 2. In arm B, the therapy will be according to the Investigator choice and managed according to local practice.

Conditions

• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	ARM A Durvalumab/chemotherapy association	NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1) ADJUVANT : 1. If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks. 2. If residual tumor at interval debulking surgery : the tremelimumab 75 mg IV will be added to the durvalumab-chemotherapy combination at day 1 of cycle 2 before a salvage surgery. Durvalumab 1125 mg IV (with one cycle of tremelimumab 75 mg IV post S3) will be pursued in maintenance treatment, up to 1 year or until disease progression, unacceptable toxicity or patient withdrawn.
DRUG	ARM B Durvalumab/Tremelimumab/chemotherapy association	NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV + tremelimumab 75 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1) ADJUVANT : 1. If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks. 2. If residual tumor at interval debulking surgery : patients will be treated according to investigator choice.

Timeline

• Start date: 2017-10-18
• Primary completion: 2024-12-31
• Completion: 2024-12-31
• First posted: 2017-08-15
• Last updated: 2025-12-03

Locations

11 sites across 1 country: France