A study of atezolizumab compared to placebo for subjects with late relapse ovarian cancer receiving a treatment with platinum-based chemotherapy and bevacizumab.
- Conditions
- Patients with epithelial ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) who have first or second late relapse (platinum-free interval > 6 months)MedDRA version: 20.0 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005471-24-ES
- Lead Sponsor
- ARCAGY-GINECO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 405
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.
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 243
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 162
E-1.Non-epithelial ovarian tumor, the fallopian tube or the peritoneum (i.e. germ cell tumors).
E-2.Ovarian tumors of low malignant potential (borderline tumors).
e-3.Synchronous primary endometrial cancer (Ca) unless a) Stage E-4.Other malignancy within last 5 years (y) except cervix or breast in situ carcinoma, breast cancer = 3y free of disease and treatment, type I stage I endometrial Ca.
E-5.Radiotherapy within 6 weeks (w) prior to study treatment.
E-6.Major surgery within 4w of starting study treatment or patients who have not completely recovered from effects of any major surgery.
E-7.Previous allogeneic bone marrow transplant or previous solid organ transplantation.
E-8.Other simultaneous chemotherapy, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous RT during treatment period (hormonal replacement therapy is permitted).
E-9.Prior treatment with CD137 agonists or immune checkpoint blockers, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
E-10.Systemic immunostimulants within 4w or 5 half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1 (D1C1).
E-11.Systemic corticosteroids or other systemic immunosuppressive medications within 2w prior to D1C1 or anticipated requirement for systemic immunosuppressors during the trial. Detailed exceptions described in study protocol.
E-12.Autoimmune disease. Detailed exceptions described in study protocol.
E-13.Idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia, or evidence of active pneumonitis. Detailed exceptions described in study protocol.
E-14.Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). Patients with active hepatitis B or hepatitis C. Detailed exceptions described in study protocol.
E-15.Signs or symptoms of infection within 2 weeks prior to D1C1.
E-16.Administration of a live, attenuated vaccine within 4w prior to C1D1, or anticipation that such a live attenuated vaccine will be required during the study.
E-17.Current or recent (within 10d 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.
E-21.Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
E-22.Left ventricular ejection fraction by MUGA/ECHO below the institutional lower limit of normal (applicable for patients intended to be treated with PLD).
E-23.Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub-Arachnoids Hemorrhage within 6m prior to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method