Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy

NCT ID: NCT02184195

Last Updated: 2023-09-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-16

Study Completion Date

2023-01-27

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Approximately 145 patients will be randomised using an Interactive Voice Response System /Interactive Web Response System (IVR/IWR system) in a 3:2 ratio (Olaparib:placebo) to the treatments as specified below:

* Olaparib tablets p.o. 300 mg twice daily
* Matching placebo tablets p.o. twice daily Eligible patients will be those patients with pancreas cancer previously treated for metastatic disease who have not progressed following completion of at least 16 weeks (can be more) of first line platinum-based chemotherapy. All patients must have a known deleterious or suspected deleterious germline BRCA mutation to be randomised; this may have been determined prior to enrolment into the study or may be assessed as part of the enrolment procedure for the study (via centrally provided MyriadIntegrated BRAC.

Patients will be randomised within 6 weeks after their last dose of chemotherapy (last dose is the day of the last infusion) and treatment started as soon as possible but no less than 4 and no more than 8 weeks of the last chemotherapy dose. At the time of starting protocol treatment, all previous chemotherapy treatment should be discontinued.

Following randomisation, patients will attend clinic visits weekly for the first 4 weeks of treatment (Days 8, 15, 22 and 29). Patients will then attend clinic visits every 4 weeks whilst on study treatment. Patients should continue to receive study treatment until objective radiological disease progression as per RECIST as assessed by the investigator and as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.

Once a patient has progressed the patient will be followed for second progression (PFS2) every 8 weeks and then survival until the final analysis.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Germline BRCA1/2 Mutations and Metastatic Adenocarcinoma of the Pancreas

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Olaparib

Olaparib tablets po. 300 mg twice daily

Group Type EXPERIMENTAL

Olaparib

Intervention Type DRUG

Tablet -100mg

Olaparib

Intervention Type DRUG

Tablet-150mg

Placebo

Placebo tablets twice daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Match Olaparib 100mg placebo

Placebo

Intervention Type DRUG

Match Olaparib 150mg placebo

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Olaparib

Tablet -100mg

Intervention Type DRUG

Olaparib

Tablet-150mg

Intervention Type DRUG

Placebo

Match Olaparib 100mg placebo

Intervention Type DRUG

Placebo

Match Olaparib 150mg placebo

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
* Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study.
* Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious
* Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator's opinion.
* Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.

Exclusion Criteria

* gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc.)
* Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
* Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle

1 Day 1 is not permitted.
* Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
* Any previous treatment with a PARP inhibitor, including Olaparib
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Myriad Genetic Laboratories, Inc.

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Gilbert, Arizona, United States

Site Status

Research Site

Orange, California, United States

Site Status

Research Site

Stanford, California, United States

Site Status

Research Site

Aurora, Colorado, United States

Site Status

Research Site

New Haven, Connecticut, United States

Site Status

Research Site

Boca Raton, Florida, United States

Site Status

Research Site

Miami, Florida, United States

Site Status

Research Site

Chicago, Illinois, United States

Site Status

Research Site

Baltimore, Maryland, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

St Louis, Missouri, United States

Site Status

Research Site

Commack, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

Columbus, Ohio, United States

Site Status

Research Site

Philadelphia, Pennsylvania, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Seattle, Washington, United States

Site Status

Research Site

Campbelltown, , Australia

Site Status

Research Site

Randwick, , Australia

Site Status

Research Site

St Leonards, , Australia

Site Status

Research Site

Antwerp, , Belgium

Site Status

Research Site

Brussels, , Belgium

Site Status

Research Site

Leuven, , Belgium

Site Status

Research Site

London, Ontario, Canada

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Sherbrooke, Quebec, Canada

Site Status

Research Site

Toronto, , Canada

Site Status

Research Site

Amiens, , France

Site Status

Research Site

Besançon, , France

Site Status

Research Site

Bordeaux, , France

Site Status

Research Site

Brest, , France

Site Status

Research Site

Clichy, , France

Site Status

Research Site

La Roche-sur-Yon, , France

Site Status

Research Site

Lille, , France

Site Status

Research Site

Lyon, , France

Site Status

Research Site

Nice, , France

Site Status

Research Site

Paris, , France

Site Status

Research Site

Paris, , France

Site Status

Research Site

Poitiers, , France

Site Status

Research Site

Strasbourg, , France

Site Status

Research Site

Toulouse, , France

Site Status

Research Site

Villejuif, , France

Site Status

Research Site

Berlin, , Germany

Site Status

Research Site

Berlin, , Germany

Site Status

Research Site

Bochum, , Germany

Site Status

Research Site

Bonn, , Germany

Site Status

Research Site

Dresden, , Germany

Site Status

Research Site

Frankfurt am Main, , Germany

Site Status

Research Site

Hamburg, , Germany

Site Status

Research Site

Hamburg, , Germany

Site Status

Research Site

Hanover, , Germany

Site Status

Research Site

Leipzig, , Germany

Site Status

Research Site

München, , Germany

Site Status

Research Site

Schweinfurt, , Germany

Site Status

Research Site

Ulm, , Germany

Site Status

Research Site

Beersheba, , Israel

Site Status

Research Site

Haifa, , Israel

Site Status

Research Site

Holon, , Israel

Site Status

Research Site

Nahariya, , Israel

Site Status

Research Site

Petah Tikva, , Israel

Site Status

Research Site

Ramat Gan, , Israel

Site Status

Research Site

Rehovot, , Israel

Site Status

Research Site

Tel Aviv, , Israel

Site Status

Research Site

Zefir, , Israel

Site Status

Research Site

Bologna, , Italy

Site Status

Research Site

Milan, , Italy

Site Status

Research Site

Milan, , Italy

Site Status

Research Site

Padua, , Italy

Site Status

Research Site

Parma, , Italy

Site Status

Research Site

Pescara, , Italy

Site Status

Research Site

Roma, , Italy

Site Status

Research Site

Roma, , Italy

Site Status

Research Site

San Giovanni Rotondo, , Italy

Site Status

Research Site

Verona, , Italy

Site Status

Research Site

Amsterdam, , Netherlands

Site Status

Research Site

Seongnam-si, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Girona, , Spain

Site Status

Research Site

L'Hospitalet de Llobregat, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Málaga, , Spain

Site Status

Research Site

Pamplona, , Spain

Site Status

Research Site

Sabadell, , Spain

Site Status

Research Site

Santiago de Compostela, , Spain

Site Status

Research Site

Valencia, , Spain

Site Status

Research Site

Zaragoza, , Spain

Site Status

Research Site

Edinburgh, , United Kingdom

Site Status

Research Site

Glasgow, , United Kingdom

Site Status

Research Site

Liverpool, , United Kingdom

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Research Site

Northwood, , United Kingdom

Site Status

Research Site

Nottingham, , United Kingdom

Site Status

Research Site

Surrey, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Belgium Canada France Germany Israel Italy Netherlands South Korea Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algul H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2.

Reference Type BACKGROUND
PMID: 31157963 (View on PubMed)

Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algul H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. doi: 10.1200/JCO.21.01604. Epub 2022 Jul 14.

Reference Type DERIVED
PMID: 35834777 (View on PubMed)

Amin S, Joo S, Nolte S, Yoo HK, Patel N, Byrnes HF, Costa-Cabral S, Johnson CD. Health-related quality of life scores of metastatic pancreatic cancer patients responsive to first line chemotherapy compared to newly derived EORTC QLQ-C30 reference values. BMC Cancer. 2022 May 20;22(1):563. doi: 10.1186/s12885-022-09661-7.

Reference Type DERIVED
PMID: 35596182 (View on PubMed)

Li N, Zheng H, Huang Y, Zheng B, Cai H, Liu M. Cost-Effectiveness Analysis of Olaparib Maintenance Treatment for Germline BRCA-Mutated Metastatic Pancreatic Cancer. Front Pharmacol. 2021 Apr 20;12:632818. doi: 10.3389/fphar.2021.632818. eCollection 2021.

Reference Type DERIVED
PMID: 33959007 (View on PubMed)

Zhan M, Zheng H, Yang Y, He Z, Xu T, Li Q. Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial. Cancer Manag Res. 2020 Dec 16;12:12919-12926. doi: 10.2147/CMAR.S283169. eCollection 2020.

Reference Type DERIVED
PMID: 33364840 (View on PubMed)

Golan T, Kindler HL, Park JO, Reni M, Macarulla T, Hammel P, Van Cutsem E, Arnold D, Hochhauser D, McGuinness D, Locker GY, Goranova T, Schatz P, Liu YZ, Hall MJ. Geographic and Ethnic Heterogeneity of Germline BRCA1 or BRCA2 Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial. J Clin Oncol. 2020 May 1;38(13):1442-1454. doi: 10.1200/JCO.19.01890. Epub 2020 Feb 19.

Reference Type DERIVED
PMID: 32073954 (View on PubMed)

Hammel P, Kindler HL, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algul H, O'Reilly EM, McGuinness D, Cui KY, Joo S, Yoo HK, Patel N, Golan T; POLO Investigators. Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib. Ann Oncol. 2019 Dec 1;30(12):1959-1968. doi: 10.1093/annonc/mdz406.

Reference Type DERIVED
PMID: 31562758 (View on PubMed)

Lowery MA, Kelsen DP, Capanu M, Smith SC, Lee JW, Stadler ZK, Moore MJ, Kindler HL, Golan T, Segal A, Maynard H, Hollywood E, Moynahan M, Salo-Mullen EE, Do RKG, Chen AP, Yu KH, Tang LH, O'Reilly EM. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018 Jan;89:19-26. doi: 10.1016/j.ejca.2017.11.004. Epub 2017 Dec 8.

Reference Type DERIVED
PMID: 29223478 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014-001589-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D081FC00001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.