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

NCT02659384 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-15082015-004601-17
• Study Type: interventional
• Target: 122
• Locations: 5 countries
• Sites: 12

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.

Conditions

Ovarian Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Bevacizumab

EXPERIMENTAL

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

atezolizumab + bevacizumab + placebo

EXPERIMENTAL

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; Drug: atezolizumab; Drug: placebo

atezolizumab + bevacizumab + acetylsalicylic acid

EXPERIMENTAL

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; Drug: atezolizumab; Drug: acetylsalicylic acid

Interventions

Bevacizumab DRUG

Also known as: Avastin

Bevacizumab; atezolizumab + bevacizumab + acetylsalicylic acid; atezolizumab + bevacizumab + placebo

atezolizumab DRUG

atezolizumab + bevacizumab + acetylsalicylic acid; atezolizumab + bevacizumab + placebo

acetylsalicylic acid DRUG

atezolizumab + bevacizumab + acetylsalicylic acid

placebo DRUG

atezolizumab + bevacizumab + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (12)

Assistance Publique - Hopitaux de Paris - Hopital Europeen Georges Pompidou

Paris, France

Location

Centre Hospitalier Privé Saint-Grégoire

Saint-Grégoire, France

Location

Academisch Medisch Centrum - Universiteit van Amsterdam

Amsterdam, Netherlands

Location

Leiden University Medical Centre

Leiden, Netherlands

Location

Radboudumc - Radboud University Medical Center Nijmegen

Nijmegen, Netherlands

Location

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

Badalona, Spain

Location

Hospital Universitario San Carlos

Madrid, Spain

Location

Centre Hospitalier Universitaire Vaudois - Lausanne

Lausanne, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

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

London, United Kingdom

Location

Royal Marsden Hospital - Chelsea, London

London, United Kingdom

Location

Royal Marsden Hospital - Sutton, Surrey

Sutton, United Kingdom

Location

Related Publications (1)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Bevacizumab; atezolizumab; Aspirin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Susana- Banerjee

  Royal Marsden Hospital - UK

  STUDY CHAIR

• George Coukos

  Centre hospitalier universitaire vaudois, Lausanne

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 20, 2016
• Study Start: December 23, 2016
• Primary Completion: June 1, 2021
• Study Completion: March 1, 2022
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

CH (2); FR (2); NL (3); ES (2); GB (3)