Status and phase
Conditions
Treatments
About
This is a phase III, randomized, double-blinded, comparative, multi-centre study to assess the efficacy of atezolizumab in combination with platinum-based chemotherapy plus bevacizumab administered concurrent to chemotherapy and in maintenance, in patients presenting epithelial ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) who have platinum-sensitive relapse (platinum-free interval > 6 months).
Full description
Approximately 600 patients will be randomized using an Interactive Voice Response System /Interactive web system (IVR/IWR system) in a 1:2 ratio to the treatments as specified below:
A. Arm A: Placebo + bevacizumab & platinum-based chemotherapy.
The placebo arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization)
B. Arm B: Atezolizumab + bevacizumab & platinum-based chemotherapy
The atezolizumab arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization)
Before randomization to the study:
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Female Patients must be ≥18 years of age.
Signed informed consent and ability to comply with treatment and follow-up.
Patients with histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma
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.
Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization:
Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
Availability at the study site of representative FFPE tumor sample from surgery during front line therapy, at best before chemotherapy
Patients must have normal organ and bone marrow function :
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
Exclusion criteria
Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
Ovarian tumors of low malignant potential (e.g. borderline tumors)
Patients with synchronous primary endometrial cancer unless both of the following criteria are met:
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).
Patients receiving radiotherapy within 6 weeks prior to study treatment.
Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1
Previous allogeneic bone marrow transplant or previous solid organ transplantation.
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).
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
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
Treatment with systemic corticosteroids or other systemic immunosuppressive medications (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
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Are eligible patients with:
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
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 Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
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
Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
Inadequately controlled HTN (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
Clinically significant (e.g. active) cardiovascular disease, including:
Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal (only applicable for patients intended to be treated with pegylated liposomal doxorubicin).
Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
History or evidence of hemorrhagic disorders within 6 months prior to randomization.
Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation).
History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
Significant traumatic injury during 4 weeks prior to randomization.
Non-healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations.
History of VEGF therapy related abdominal fistula or gastrointestinal perforation.
Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.
Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.
Women of childbearing potential (<2 years after last menstruation and not surgically sterile) not willing to use highly-effective means of contraception (Appendix 1) during the study and for 6 months after the last dose of study medication
Pregnant or lactating women.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation.
Known hypersensitivity reaction or allergy to drugs chemically related to bevacizumab, carboplatin, gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or their excipients that contraindicates the subject's participation
Primary purpose
Allocation
Interventional model
Masking
614 participants in 2 patient groups, including a placebo group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal