NCT02184195

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
154

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Dec 2014

Longer than P75 for phase_3

Geographic Reach
12 countries

103 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 6, 2014

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 9, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

December 16, 2014

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2019

Completed
1 year until next milestone

Results Posted

Study results publicly available

January 27, 2020

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2023

Completed
Last Updated

September 13, 2023

Status Verified

June 1, 2023

Enrollment Period

4.1 years

First QC Date

June 6, 2014

Results QC Date

January 14, 2020

Last Update Submit

August 18, 2023

Conditions

Keywords

BRCA, metastatic adenocarcinoma pancreas, maintenance olaparib monotherapy, first line platinum chemotherapy, pancreatic cancer, PARP inhibitor

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Using Modified Response Evaluation Criteria in Solid Tumours. This Study Used Modified RECIST Version (v) 1.1 (RECIST v1.1)

    To determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.

    Up to 4 years

Secondary Outcomes (9)

  • Overall Survival (OS)

    Upto 4 years

  • Time From Randomisation to Second Progression (PFS2)

    Up to 4 years

  • Time From Randomisation to Second Subsequent Therapy or Death (TSST)

    Up to 4 years

  • Time From Randomisation to First Subsequent Therapy or Death (TFST)

    Up to 4 years

  • Time From Randomisation to Study Treatment Discontinuation or Death (TDT)

    Up to 4 years

  • +4 more secondary outcomes

Study Arms (2)

Olaparib

EXPERIMENTAL

Olaparib tablets po. 300 mg twice daily

Drug: Olaparib

Placebo

PLACEBO COMPARATOR

Placebo tablets twice daily

Drug: Placebo

Interventions

Tablet -100mg

Olaparib

Match Olaparib 100mg placebo

Placebo

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (103)

Research Site

Gilbert, Arizona, 85234, United States

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Orange, California, 92868, United States

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Stanford, California, 94305-5720, United States

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Aurora, Colorado, 80045, United States

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New Haven, Connecticut, 06510, United States

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Boca Raton, Florida, 33486, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02215, United States

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St Louis, Missouri, 63110, United States

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Commack, New York, 11725, United States

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New York, New York, 10016, United States

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New York, New York, 10022, United States

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New York, New York, 10032, United States

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New York, New York, 10065, United States

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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19111, United States

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Houston, Texas, 77030, United States

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Seattle, Washington, 98104, United States

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Campbelltown, 2560, Australia

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Randwick, 2031, Australia

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St Leonards, 2065, Australia

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Antwerp, 2020, Belgium

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Brussels, 1070, Belgium

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Leuven, 3000, Belgium

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London, Ontario, N6A 4L6, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Sherbrooke, Quebec, J1G 2E8, Canada

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Toronto, M5G 2M9, Canada

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Amiens, 80054, France

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Besançon, 25000, France

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Bordeaux, 33075, France

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Brest, 29609, France

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Clichy, 92118, France

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La Roche-sur-Yon, 85925, France

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Lille, 59020, France

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Lyon, 69437, France

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Nice, 06189, France

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Paris, 75014, France

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Paris, 75674, France

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Poitiers, 86021, France

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Strasbourg, 67065, France

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Toulouse, 31059, France

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Villejuif, 94800, France

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Berlin, 10967, Germany

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Berlin, D-13353, Germany

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Bochum, 44791, Germany

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Bonn, 53127, Germany

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Dresden, 01307, Germany

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Frankfurt am Main, 60596, Germany

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Hamburg, 20246, Germany

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Hamburg, 22291, Germany

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Hanover, 30625, Germany

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Leipzig, 04103, Germany

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München, 81675, Germany

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Schweinfurt, 97422, Germany

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Ulm, 89081, Germany

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Beersheba, 84101, Israel

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Haifa, 3109601, Israel

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Holon, 58100, Israel

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Nahariya, 22100, Israel

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Petah Tikva, 4941492, Israel

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Ramat Gan, 5265601, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 6423906, Israel

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Zefir, 7030000, Israel

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Bologna, 40138, Italy

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Milan, 20132, Italy

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Milan, 20133, Italy

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Padua, 35128, Italy

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Parma, 43126, Italy

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Pescara, 65100, Italy

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Roma, 00128, Italy

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Roma, 00144, Italy

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San Giovanni Rotondo, 71013, Italy

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Verona, 37134, Italy

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Amsterdam, 1105 AZ, Netherlands

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Seongnam-si, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 6351, South Korea

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Barcelona, 08035, Spain

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Girona, 17007, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Madrid, 28050, Spain

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Málaga, 29010, Spain

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Pamplona, 31008, Spain

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Sabadell, 8208, Spain

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Santiago de Compostela, 15706, Spain

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Valencia, 46009, Spain

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Zaragoza, 50009, Spain

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Edinburgh, EH4 2XR, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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Liverpool, L69 3GA, United Kingdom

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London, SE5 9RS, United Kingdom

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London, WC1E 6AG, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Surrey, SM1 2DL, United Kingdom

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Related Publications (8)

  • 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.

    PMID: 31157963BACKGROUND
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Results Point of Contact

Title
Global Clinical Leader
Organization
AstraZeneca AB

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

June 6, 2014

First Posted

July 9, 2014

Study Start

December 16, 2014

Primary Completion

January 15, 2019

Study Completion

January 27, 2023

Last Updated

September 13, 2023

Results First Posted

January 27, 2020

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, 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.
More information

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