Immunotherapy With Neo-adjuvant Chemotherapy for OVarian Cancer

NCT03249142 | Completed Phase 1 DMC

• 1 other identifier: GINECO-OV127b
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer; Anti-PD-L1; Anti-CLA-4; Neo-adjuvant

Outcome Measures

Primary Outcomes (1)

• Toxicity after neo-adjuvant treatment

  frequency of adverse events according to CTCAE v4.03 criteria

  At the end of cycle 3 (each cycle is 21 days)

Secondary Outcomes (7)

• Toxicity after adjuvant treatment

  At the end of cycle 6 (each cycle is 21 days)

• Toxicity after maintenance therapy

  Up to 18 months

• Safety after interval debulking surgery

  Up to 6 months

• Progression Free Survival (PFS) based on investigator assessment using the RECIST version 1.1

  From date of randomisation until the date of progression or death, which ever occurs earlier, assessed up to 36 months

• Sugarbaker Peritoneal Index Score (PCI)

  Up to 6 months

Study Arms (2)

ARM A Durvalumab/chemotherapy association

EXPERIMENTAL

Drug: ARM A Durvalumab/chemotherapy association

ARM B Durvalumab/Tremelimumab/chemotherapy association

EXPERIMENTAL

Drug: ARM B Durvalumab/Tremelimumab/chemotherapy association

Interventions

ARM A Durvalumab/chemotherapy association DRUG

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.

ARM A Durvalumab/chemotherapy association

ARM B Durvalumab/Tremelimumab/chemotherapy association DRUG

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.

ARM B Durvalumab/Tremelimumab/chemotherapy association

Eligibility Criteria

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

You may qualify if:

• I-1 Female patients must be ≥ 18 years of age. I-2 Signed informed consent and ability to comply with treatment and follow-up. I-3 Patients with newly histologically confirmed epithelial ovarian cancer (or fallopian tube or primary peritoneal adenocarcinoma).
• I-4 Advanced FIGO stage IIIC to IV. I-5 Patients for whom primary debulking surgery has been denied after an evaluation through laparoscopy or laparotomy.
• I-6 Patient for whom a neo-adjuvant strategy has been planned. I-7 Interval between diagnosis and enrolment (informed consent signed) ≤ 8 weeks.
• I-8 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. I-9 Geriatric vulnerability score (GVS) \< 3 for patients ≥ 70 years. I-10 Adequate organ and bone marrow function. I-11 Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) ≤ 1.5 and an Activated ProThrombin Time (aPTT) ≤ 1.5 x ULN. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to site medical standard) and if the patient is on a stable dose of anticoagulants for at least two weeks at the time of randomization.
• I-12 As this study will include patients in France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social category.

You may not qualify if:

• E-1 Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS).
• E-2 Major surgical procedure (defined by the resection of at least one organ including ovary) within 28 days prior to the first dose.
• E-3 Any concurrent chemotherapy, investigational product, biological, or hormonal therapy for cancer treatment.
• E-4 Previous treatment with immunotherapy, including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, or therapeutic anticancer vaccine.
• E-5 Active or prior documented autoimmune or inflammatory disorders The following are exceptions to this criterion:
• Patients with vitiligo or alopecia,
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment.
• E-6 Current/prior immunosuppressive medication ≤ 14 days before first durvalumab and tremelimumab dose (including, but not limited to, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.
• E-7 Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible.
• E-8 Uncontrolled diabetes mellitus, uncontrolled hypothyroidism. E-9 Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half- lives of the drug (whichever is shorter) prior to Cycle 1, Day 1.
• E-10 History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis. Radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted.
• E-11 Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. E-12 Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza.
• E-13 Current or recent (within 10 days prior to randomization) chronic use of aspirin \> 325 mg/day.
• E-14 Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
• E-15 Inadequately controlled HTN (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications).

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• AstraZeneca: collaborator

Study Sites (11)

Institut Ste Catherine

Avignon, France

Location

Institut Bergonié

Bordeaux, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Groupe confluent

Nantes, 44202, France

Location

HEGP

Paris, France

Location

Hôpital Cochin

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut René Godinot

Reims, France

Location

Centre Eugene Marquis

Rennes, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Ovarian Neoplasms

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

Study Officials

• Alexandra LEARY, MD, PhD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 15, 2017
• Study Start: October 18, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)