Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Relapsed Ovarian Cancer; Following Complete or Partial Response to Platinum Based Chemotherapy; BRCA Mutated; Platinum Sensitive

Treatments: Drug: Placebo to match olaparib 300mg; Drug: Olaparib 300mg tablets

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01874353

D0816C00002

2013-001211-75 (EudraCT Number)

Details and patient eligibility

About

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

Full description

Comparison of olaparib against a placebo in patients with ovarian cancer whose cancer has already improved by taking platinum based chemotherapy. The patients must also have a fault in their DNA which codes for the BRCA protein. The BRCA protein helps mend broken DNA in the cells of the body; if this protein doesn't work properly it can increase the chance of getting cancer. The aim of this study is to see whether patients taking olaparib tablets last longer until their cancer gets worse, compared to those taking the placebo tablet. The study is also looking to see if there is an overall improvement to how long the patients survive whilst taking olaparib tablets compared to the placebo tablets; and the quality of their life whilst living with ovarian cancer.

Enrollment: 327 patients

Sex: Female

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must be ≥ 18 years of age.

  • Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
  • Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
  • Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation

For the penultimate chemotherapy course prior to enrolment on the study:

• Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy

For the last chemotherapy course immediately prior to randomisation on the study:

• Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course
• Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
• Patients must be randomized within 8 weeks of their last dose of chemotherapy
• Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab

Exclusion criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism" etc.)
• Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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327 participants in 2 patient groups, including a placebo group

Olaparib 300mg tablets

Experimental group

Description:

Taken orally twice daily

Treatment:

Drug: Olaparib 300mg tablets

Placebo tablets

Placebo Comparator group

Description:

Taken orally twice daily

Treatment:

Drug: Placebo to match olaparib 300mg