Tri Association in Patient With Advanced Epithelial Ovarian Cancer in Relapse — BOLD  

Epithelial Ovarian Cancer Clinical Trial

Official title: A GINECO Phase II Trialo Assessing the Safety and the Efficacy of the Bevacizumab, Olaparib and Durvalumab (MEDI 4736) Combination in Patients With Advanced Epithelial Ovarian Cancer in Relapse

Status Active, not recruiting

Clinical Trial Summary

Assessing the safety and efficacy of the bevacizumab, Olaparib and Durvalumab (MEDI 4736) combination in patient with high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor, with at least one previous line of platinum-taxane chemotherapy, and present with platinum resistant disease (PRR) or platinum-sensitive relapse (PSR), whatever the line of chemotherapy given at relapse.

Clinical Trial Description

Bevacizumab and olaparib have already been tested on 12 patients in a phase I trial at their usual doses (10 mg/kg q2w and 400 mg bid - 50 mg capsules -, respectively), and no DLTs were observed. The addition of an anti-VEGF small molecule, cediranib, to olaparib doubled the median PFS in a randomized phase II trial in patients with platinum sensitive relapse, with a manageable safety profile.

A recently reported phase I trial established the RDP2D of Durvalumab and Olaparib - 150 mg tablets -, when given in combination, at 1500 mg every 4 weeks, and 300 mg bid, respectively. In addition, the ENGOT/GINECO PAOLA phase III trial is currently evaluating the combination of Olaparib and Bevacizumab as first-line maintenance after platinum-paclitaxel combination, in patients with advanced high-grade serous ovarian carcinoma. Under the hypothesis of a survival benefit in favor of this combination, it would also be of interest to assess the value of adding Durvalumab in order to improve the efficacy of the overall combination.

There are no trials to date assessing anti-VEGF in combination with anti-PARP and anti-PD-L1 therapy.

Beside additive efficacy, a synergistic effect could be expected :

• Between bevacizumab and durvalumab, through normalization of blood vessel and potentiation of immunologic infiltration.

• Between olaparib and durvalumab, through cytotoxicity-mediated release of antigens and impairment of mutation repair mechanisms, thereby increasing neoantigen loads.

• Between olaparib and bevacizumab, through tumor environment modulation and signaling of DNA damage inhibition, which has already been tested with the anti-VEGF cediranib.

For those reasons the sponsor propose a phase II trial of Olaparib, Bevacizumab and Durvalumab combination, in patients with relapsing AO high grade carcinoma :

• In platinum sensitive relapse (PSR), whatever the line, in patients not amenable to frontline surgery of the relapse and previously-treated by a platinum-containing chemotherapy in first line and

• Either didn't receive any of the tested drugs,

• Or previously received either bevacizumab or olaparib BUT NOT the combination of both drugs.

• In platinum-resistant relapse (PRR), in previously untreated patients for their relapse, or in patients who received a maximum of 1 chemotherapy regimen in this setting and either

• Either didn't receive any of the tested drugs,

• Or previously received either bevacizumab or olaparib BUT NOT the combination of both drugs.

The trial will also propose translational research, including :

• Assessment of germline and somatic BRCA mutations and determination of HRD phenotype and mutational load by NGS

• Quantification of mutagenesis in simultaneous treatment on ctDNA

• Characterization of immune response in the tumor by Nanostring immuno-oncology panel on tumors ;

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Ovarian Neoplasms
• Recurrence
• Relapse

• NCT number: NCT04015739
• Study type: Interventional
• Source: ARCAGY/ GINECO GROUP
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 1, 2019
• Completion date: January 29, 2024