A study of atezolizumab compared to placebo for subjects with late relapse ovarian cancer receiving a treatment with platinum-based chemotherapy and bevacizumab.

Phase 1

• Conditions: Patients with late relapse of epithelial ovarien cancer, fallopian tube or peritoneal cancer treated with chemotherapy , bevacizumab and a anti PD-L1; MedDRA version: 20.0Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005471-24-AT
• Lead Sponsor: ARCAGY-GINECO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-11-09
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 600

Inclusion Criteria

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 histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma
I-4. Patients with PD-L1 status determined for stratification on mandatory de novo biopsy sent to central laboratory as a formalin-fixed, paraffin-embedded (FFPE) sample.
- Cell pellet from pleural effusion, or ascites or lavage are not acceptable.
- For core needle biopsy specimens, at least three cores should be obtained. Biopsies must be obtained in a manner that minimizes risks for the patient and maximizes the chance to get tumor tissue. In case the core biopsies do not contain significant tumor tissue, patient eligibility should be discussed with the sponsor

I-5. Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization:
a) criterion for relapse can be according to RECIST v1.1, CA125 (GCIG) or clinical symptoms
b) the interval between last dose of platinum and entry in the study should be free of new anti-cancer treatment, with the exception of a maintenance therapy which is allowed up to 21 days before study entry.
I-6. Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
I-7.Availability at the study site of representative FFPE archival tumor sample from surgery during front-line therapy, at best before chemotherapy
I-8. Patients must have normal organ and bone marrow function :
a) Haemoglobin = 10.0 g/dL.
b) Absolute neutrophil count (ANC) = 1.5 x 109/L.
c) Platelet count = 100 x 109/L.
d) Total bilirubin = 1.5 x institutional upper limit of normal (ULN).
e) Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN, unless liver metastases are present in which case they must be = 5 x ULN.
f) Serum creatinine = 1.5 x institutional ULN,
g) 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.
h) Urine dipstick for proteinuria < 2+. If urine dipstick is =2+, 24-hours urine must demonstrate =1 g of protein in 24 hours.
i) Normal blood pressure or adequately treated and controlled hypertension (systolic BP = 150mmHg and diastolic BP =100mmHg).
I-9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240

Exclusion Criteria

E-1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
E-2. Ovarian tumors of low malignant potential (e.g. borderline tumors)
E-3. Patients with synchronous primary endometrial cancer unless both of the following criteria are met:
a) stage < II,
b) Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR = 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1or 2 endometrioid adenocarcinoma.
c) Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
E-4. Other malignancy within the last 5 years except cervix or breast in situ carcinoma, breast cancer = 3 years free of disease and treatment, type I stage I endometrial cancer.
E-5. Patients receiving radiotherapy within 6 weeks prior to study treatment.
E-6.Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery.
E-7. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
E-8. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
E-9. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
E-10. Treatment with systemic immunostimulatory agents
E-11. Treatment with systemic corticosteroids or other systemic immunosuppressive medications.
a) The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
b) Prophylactic anti-emetic corticosteroids will be avoided if possible in patients treated with pegylated liposomal doxorubicin-carboplatin or gemcitabine-carboplatin regimen. The use of corticosteroids is allowed as premedication for paclitaxel-based regimen and/or premedication in case of carboplatin hypersensitivity.
E-12. History of autoimmune disease
E-13. 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-14. Immunocompromised patients,
E-15. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
E-16. 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.
E-17. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
E-18. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
E-19. Inadequately controlled HTN
E-20. Clinically significant (e.g. active) cardiovascular disease, including:
a) Myocardial infarction or unstable angina within = 6 months of randomization,
b) New York Heart Association (NYHA) = grade 2 congestive heart failure (CHF),
c) Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified