Olaparib maintenance treatment versus placebo in patients with PSR Ovarian Cancer who are in CR or PR to platinum-based chemotherapy and whose tumours carry sBRCAm or HRR-associated genes mutations

Study identifier:D0816C00009

ClinicalTrials.gov identifier:NCT02392676

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients with Platinum Sensitive Relapsed Ovarian Cancer who are in Complete or Partial Response Following Platinum Based Chemotherapy and whose tumours Carry Loss of Function Somatic BRCA Mutation(s) or Loss of Function Mutation(s) in tumour Homologous Recombination Repair –Associated Genes

Medical condition

Platinum Sensitive Relapsed Ovarian Cancer

Phase

Phase 3

Healthy volunteers

Study drug

OLAPARIB, PLACEBO

Sex

Female

Actual Enrollment

Study type

Interventional

Age

18 Years - 96 Years

Date

Study Start Date: 01 Jul 2016

Estimated Primary Completion Date: 01 Jun 2019

Estimated Study Completion Date: 01 Jun 2019

Study design

Allocation: Randomized
Endpoint Classification: Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2016 by AstraZeneca

Collaborators

Myriad Genetics - BRCA Analysis test for FDA Premarket Approval (PMA)

Inclusion and exclusion criteria

Inclusion Criteria

- Patients must be ≥ 18 years of age
- Histologically diagnosed relapsed high grade epithelial ovarian cancer (including primary peritoneal and/ or fallopian tube cancer)
- Documented deleterious or suspected deleterious somatic BRCA 1 and/or BRCA 2 somatic mutation or evidence of non- BRCA HRR-associated gene mutation in the tumour.
- At least 2 previous lines of platinum containing therapy prior to randomisation.
- CA-125 measurements prior to randomised treatment
- Patients must have normal organ and bone marrow function measured within 28 days of randomisation
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
- Provision of a blood sample for cfDNA biomarker analysis in Pre-Screening Part 1
- Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary or recurrent cancer must be available for central testing. If archival tumour sample is not available tumour sample from fresh biopsy is acceptable, for all patients eligible to participate in Pre-Screening part 2.

Exclusion Criteria

- Documented germline mutation in BRCA1 and/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 had drainage of their ascites from the final 2 cycles of their last chemotherapy regimen prior to randomisation on the study
- Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to randomisation
- Any previous treatment with a PARP inhibitor, including olaparib
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product
- Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply)
- Patients receiving any systemic chemotherapy (including chemotherapy received as the most recent anticancer therapy) or radiotherapy (except for palliative reasons) within 3 weeks prior to study randomised treatment
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) CTCAE grade 2) caused by previous cancer therapy, excluding CTCAE grade 2 peripheral neuropathy
- Patients with myelodysplastic syndrome/acute myeloid leukaemia (t-AML) or with features suggestive of MDS/AML
- Patients with symptomatic uncontrolled brain metastases
- Major surgery within 2 weeks of starting study randomised treatment and patients must have recovered from any effects of any major surgery
- Patients considered a poor medical risk

No locations available

Arms	Assigned Interventions
Experimental: 1/OLAPARIB olaparib 300 mg oral tablets; twice daily	Drug: OLAPARIB Patients should continue with therapy until objective radiological disease progression as per RECIST 1.1 despite rises in CA-125. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria
Placebo Comparator: 2/PLACEBO placebo matching olaparib 300 mg oral tablets; twice daily	Drug: PLACEBO Patients should continue with therapy until objective radiological disease progression as per RECIST 1.1 despite rises in CA-125. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Charlie Gourley

University of Edinburgh