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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 2

Conditions: Ovarian Neoplasms

Treatments: Drug: acetylsalicylic acid; Drug: placebo; Drug: Bevacizumab; Drug: atezolizumab

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02659384

EORTC-1508

2015-004601-17 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 122 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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122 participants in 3 patient groups

Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Bevacizumab

atezolizumab + bevacizumab + placebo

Experimental group

Description:

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.

Treatment:

Drug: atezolizumab

Drug: placebo

Drug: Bevacizumab

atezolizumab + bevacizumab + acetylsalicylic acid

Experimental group

Description:

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.

Treatment:

Drug: atezolizumab

Drug: Bevacizumab

Drug: acetylsalicylic acid