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

Phase 2
Completed
Conditions
Ovarian Neoplasms
Interventions
Registration Number
NCT02659384
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
122
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.

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
atezolizumab + bevacizumab + placeboatezolizumabThe 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.
atezolizumab + bevacizumab + placeboplaceboThe 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.
atezolizumab + bevacizumab + acetylsalicylic acidatezolizumabThe 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.
BevacizumabBevacizumabBevacizumab 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.
atezolizumab + bevacizumab + placeboBevacizumabThe 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.
atezolizumab + bevacizumab + acetylsalicylic acidBevacizumabThe 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.
atezolizumab + bevacizumab + acetylsalicylic acidacetylsalicylic acidThe 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.
Primary Outcome Measures
NameTimeMethod
Progression free survival (PFS) at 6 months assessed by Response Evaluation Criteria in Solid Tumors (RECIST)6 months

Progression Free Survival at 6 months assessed by local investigator

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (12)

Leiden University Medical Centre

🇳🇱

Leiden, Netherlands

Centre Hospitalier Universitaire Vaudois

🇨🇭

Lausanne, Switzerland

Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital

🇬🇧

London, United Kingdom

Assistance Publique - Hopitaux de Paris - Hopital Europeen Georges Pompidou

🇫🇷

Paris, France

Royal Marsden Hospital - Sutton, Surrey

🇬🇧

Sutton, United Kingdom

Hospital Universitario San Carlos

🇪🇸

Madrid, Spain

Centre Hospitalier Privé Saint-Grégoire

🇫🇷

Saint-Grégoire, France

Academisch Medisch Centrum - Universiteit van Amsterdam

🇳🇱

Amsterdam, Netherlands

Radboudumc - Radboud University Medical Center Nijmegen

🇳🇱

Nijmegen, Netherlands

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

🇪🇸

Badalona, Spain

Royal Marsden Hospital - Chelsea, London

🇬🇧

London, United Kingdom

Centre Hospitalier Universitaire Vaudois - Lausanne

🇨🇭

Lausanne, Switzerland

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