Anti-programmed Cell Death-1 Ligand 1 (aPDL-1) Antibody Atezolizumab, Bevacizumab and Acetylsalicylic Acid in Recurrent Platinum Resistant Ovarian Cancer

Study Overview
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Brief Summary
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This is a randomized phase II study, aimed at evaluating the efficacy (through progression free survival at 6 months) and safety of 5 different treatments involving atezolizumab, bevacizumab and/or acetylsalicylic acid in advanced recurrent platinum-resistant ovarian cancer patients in order to select the optimal treatments for further development in Phase III.

Official Title
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A Phase II Study of the Anti-PDL1 Antibody Atezolizumab, Bevacizumab and Acetylsalicylic Acid to Investigate Safety and Efficacy of This Combination in Recurrent Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: atezolizumab
* Drug: acetylsalicylic acid
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent, histologically proven, platinum-resistant, epithelial ovarian, fallopian tube and primary peritoneal cancer in advanced or metastatic stage. Histological diagnosis by image guided biopsy, laparoscopy or laparotomy. Tumors diagnosed on cytology only and borderline tumors are excluded. At least one lesion accessible to biopsy without putting patient at risk WHO PS: 0-2 for patients having received no more than two previous lines of therapy. WHO PS: 0-1 for patients having received >2 previous lines of therapy Prior chemotherapy or bevacizumab: Any number of platinum-based chemotherapy lines are allowed but a maximum of 2 previous non-platinum containing lines Prior treatment with bevacizumab or other targeted agents against Vascular Endothelial Growth Factor (VEGF) or VEGF receptor is allowed, but at least 18 weeks must have elapsed since their last administration Eligible patients with ≤ 2 previous treatment lines must have been previously exposed to bevacizumab or other targeted agents against VEGF or VEGF receptor Patients may have had prior therapy providing the following conditions are met: Radiation therapy: wash-out period of 14 days prior to the first study treatment; exception: single fraction radiotherapy with the indication of pain control Systemic anti-tumor therapy: wash-out period of 21 days prior to the first study treatment Recovery from any toxic effects of prior therapy to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) except fatigue or alopecia. Exclusion criteria: Age <18 years Life expectancy of < 12 weeks No adequate hematologic and end organ function Use of acetylsalicylic acid, NSAIDs or other COX-2 inhibitors that cannot be stopped at baseline and for the whole duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab<br>Bevacizumab monotherapy treatment in arm 1 will be discontinued upon RECIST documented progression or upon treatment withdrawal, whichever occurs first. Patients will cross-over to the combination of bevacizumab and atezolizumab upon progression as long as they meet cross-over criteria. | Drug: Bevacizumab<br> <br> * Other names: Avastin;|
| Experimental: atezolizumab + bevacizumab + placebo<br>The randomized treatment regimen (atezolizumab + bevacizumab + placebo) will be continued until treatment failure or upon treatment withdrawal, whichever occurs first. Patients then go off protocol treatment and further treatment is left to the investigator's decision. | Drug: Bevacizumab<br> <br> * Other names: Avastin;Drug: atezolizumab<br> <br> Drug: placebo<br> <br> |
| Experimental: atezolizumab + bevacizumab + acetylsalicylic acid<br>The randomized treatment regimen (atezolizumab + bevacizumab + acetylsalicylic acid) will be continued until treatment failure or upon treatment withdrawal, whichever occurs first. Patients then go off protocol treatment and further treatment is left to the investigator's decision. | Drug: Bevacizumab<br> <br> * Other names: Avastin;Drug: atezolizumab<br> <br> Drug: acetylsalicylic acid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) at 6 months assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Progression Free Survival at 6 months assessed by local investigator | 6 months |