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

NCT02392676 | Withdrawn Phase 3 DMC

• 1 other identifier: D0816C00009
• Study Type: interventional
• Target: N/A
• Locations: 5 countries
• Sites: 29

Brief Summary

Olaparib administered as monotherapy in the maintenance setting improves progression free survival compared to placebo in patients whose tumours carry loss of function (deleterious or suspected deleterious) somatic BRCA mutations or loss of function (deleterious or suspected deleterious) mutation in non-BRCA Homologous Recombination Repair (HRR) -associated genes who have a complete or partial response to platinum-based chemotherapy.

Conditions

Platinum Sensitive Relapsed Ovarian Cancer

Keywords

Ovarian cancer; Platinum; Somatic BRCA mutation; Homologous recombination repair

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) using modified RECIST 1.1 in the cohort of patients with sBRCA ovarian cancer

  To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of progression free survival (PFS) using blinded independent central review (BICR)

  From date of randomization until the date of first documented progression or date of death (by any cause, in the absence of disease progression) whichever came first, assessed up to 40 months

Secondary Outcomes (9)

• Progression Free Survival (PFS) using modified RECIST 1.1. in the Intent to Treat Population (ITT) consisting of all randomised patients with sBRCAm or HRR-associated gene mutations

  From date of randomization until the date of first documented progression or date of death (by any cause, in the absence of disease progression), whichever came first, assessed up to 60 months

• Overall Survival (OS) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients

  From the date of randomisation until death due to any cause, assessed up to 60 months

• Time from randomisation to first subsequent therapy or death (TFST) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients

  From the date of randomisation to the earlier of first subsequent therapy start date, assessed up to 60 months

• Trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in sBRCA and HRR associated gene mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy

  Administered at baseline, at day 29 then every 8 weeks (+/- 1 week) regardless of treatment discontinuation or disease progression, assessed up to 24 months

• Plasma mutation status

  cfDNA sample collected during pre-screening, assessed up to 40 months

Other Outcomes (4)

• Number of AEs in all patients who received at least one dose of randomised investigational product, olaparib or placebo

  assessed up to 60 months

• Changes in Vital signs in all patients who received at least one dose of randomised investigational product, olaparib or placebo

  assessed up to 60 months

• Changes in Physical examination results in all patients who received at least one dose of randomised investigational product, olaparib or placebo

  assessed up to 60 months

Study Arms (2)

1/OLAPARIB

EXPERIMENTAL

olaparib 300 mg oral tablets; twice daily

Drug: OLAPARIB

2/PLACEBO

PLACEBO COMPARATOR

placebo matching olaparib 300 mg oral tablets; twice daily

Drug: PLACEBO

Interventions

OLAPARIB DRUG

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

1/OLAPARIB

PLACEBO DRUG

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

2/PLACEBO

Eligibility Criteria

• Age: 18 Years - 96 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Myriad Genetic Laboratories, Inc.: collaborator

Study Sites (29)

Research Site

Mobile, Alabama, United States

Location

Research Site

Phoenix, Arizona, United States

Location

Research Site

Los Angeles, California, United States

Location

Research Site

Stanford, California, United States

Location

Research Site

Augusta, Georgia, United States

Location

Research Site

Park Ridge, Illinois, United States

Location

Research Site

Iowa City, Iowa, United States

Location

Research Site

Louisville, Kentucky, United States

Location

Research Site

Covington, Louisiana, United States

Location

Research Site

Scarborough, Maine, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Albany, New York, United States

Location

Research Site

Oklahoma City, Oklahoma, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Milwaukee, Wisconsin, United States

Location

Research Site

Chiclayo, Peru

Location

Research Site

Lima, Peru

Location

Research Site

Quezon City, Philippines

Location

Research Site

Goyang-si, South Korea

Location

Research Site

Seongnam-si, South Korea

Location

Research Site

Seoul, South Korea

Location

Research Site

Birmingham, United Kingdom

Location

Research Site

Cambridge, United Kingdom

Location

Research Site

Coventry, United Kingdom

Location

Research Site

Edinburgh, United Kingdom

Location

Research Site

London, United Kingdom

Location

Research Site

Manchester, United Kingdom

Location

Research Site

Oxford, United Kingdom

Location

Research Site

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib

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

Study Officials

• Charlie Gourley, Prof.

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Carol Aghajanian, MD

  MSKCC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: March 19, 2015
• Study Start: July 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: May 2, 2016

Record last verified: 2016-04

Locations

PH (1); PE (2); KR (3); GB (8); US (15)