Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats

• ClinicalTrials.gov Identifier: NCT01078662
• Recruitment Status: Active, not recruiting
• First Posted: March 2, 2010
• Results First Posted: May 22, 2015
• Last Update Posted: April 8, 2022
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

To assess the efficacy of oral olaparib in patients with advanced cancer who have a confirmed genetic BRCA1 and/or BRCA2 mutation, by assessment of tumour response.

Condition or disease	Intervention/treatment	Phase
Ovarian; Breast; Prostate; Pancreatic; Advanced Tumours	Drug: olaparib	Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 298 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation
• Actual Study Start Date: February 21, 2010
• Actual Primary Completion Date: July 31, 2012
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: 1; Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions.

Drug: olaparib; Tablets Oral BID; Other Name: Lynparza

Outcome Measures

Primary Outcome Measures :

1. Tumour Response Rate [ Time Frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months ]
   Tumour response rate is the proportion of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

Secondary Outcome Measures :

1. Objective Response Rate [ Time Frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months ]
   Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
2. Progression Free Survival [ Time Frame: Tumour assessments are carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months ]
   Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit.
3. Overall Survival [ Time Frame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months ]
   Overall survival is defined as the duration from first dose till death. In absence of death, the time is calculated from first dose till the date subject last known to be alive.
4. Overall Survival Rate at 12 Months [ Time Frame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months ]
   Overall survival rate at 12 months is defined as the proportion of patients who are alive 12 months after date of first dose
5. Duration of Response [ Time Frame: From onset of first occurrence of complete or partial response till documented progression or death by any cause in the absence of progression, assessed maximum up to 29 months ]
   Duration of response is calculated from the date of first documented response (complete or partial) until date of documented progression (as defined by RECIST 1.1) or death (by any cause) in the absence of disease progression.
6. Disease Control Rate at Week 16 [ Time Frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then at week 8 and week 16 ]
   Disease control rate is the proportion of patients with best response of complete or partial response or stable disease according to definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) till week 16.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 130 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed documented deleterious or suspected deleterious BRCA mutation. (The presence of a loss-of-function germline mutation in the BRCA1 and/or BRCA2 gene must be confirmed prior to consent according to local practice).
• Confirmed malignant solid tumours for which no standard treatment exists
• At least one lesion (measurable and/or non measurable) at baseline that can be accurately assessed by CT/MRI and is suitable for repeated assessment at follow up visits

Exclusion Criteria:

• Any previous treatment with a PARP inhibitor, including olaparib
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Patients receiving any systematic chemotherapy, radiotherapy (except for palliative reasons) within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used)

Contacts and Locations

Locations

United States, California

Research Site

West Hollywood, California, United States, 90048

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19104

Australia

Research Site

Melbourne, Australia, 3000

Research Site

Randwick, Australia, 2031

Germany

Research Site

Köln, Germany, 50931

Israel

Research Site

Haifa, Israel, 31096

Research Site

Haifa, Israel, 35152

Research Site

Jerusalem, Israel, 91031

Research Site

Jerusalem, Israel, 91120

Research Site

Petah Tikva, Israel, 49100

Research Site

Ramat Gan, Israel, 52621

Research Site

Tel-Aviv, Israel

Spain

Research Site

Madrid, Spain, 08035

Sweden

Research Site

Lund, Sweden, 221 85

Sponsors and Collaborators

AstraZeneca

Investigators

• Study Director: Jane Robertson, BSc, MBCHB, MD; AstraZeneca
• Principal Investigator: Bella Kaufman, MD; Chaim Sheba Medical Centre, Tel Hashomer, Israel

More Information

Additional Information:

Protocol redacted 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.

Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203. doi: 10.1016/j.ygyno.2015.12.020. Epub 2015 Dec 23.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01078662
• Other Study ID Numbers: D0810C00042
• First Posted: March 2, 2010
• Results First Posted: May 22, 2015
• Last Update Posted: April 8, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Keywords provided by AstraZeneca:

olaparib; PARP inhibitors; genetic BRCA1 mutation; BRCA2 mutation; solid tumour refractory

Additional relevant MeSH terms:

Olaparib; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents