Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02184195




Registration number
NCT02184195
Ethics application status
Date submitted
6/06/2014
Date registered
9/07/2014
Date last updated
13/09/2023

Titles & IDs
Public title
Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
Scientific title
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
Secondary ID [1] 0 0
2014-001589-85
Secondary ID [2] 0 0
D081FC00001
Universal Trial Number (UTN)
Trial acronym
POLO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Germline BRCA1/2 Mutations and 0 0
Metastatic Adenocarcinoma of the Pancreas 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaparib
Treatment: Drugs - Olaparib
Treatment: Drugs - Placebo
Treatment: Drugs - Placebo

Experimental: Olaparib - Olaparib tablets po. 300 mg twice daily

Placebo comparator: Placebo - Placebo tablets twice daily


Treatment: Drugs: Olaparib
Tablet -100mg

Treatment: Drugs: Olaparib
Tablet-150mg

Treatment: Drugs: Placebo
Match Olaparib 100mg placebo

Treatment: Drugs: Placebo
Match Olaparib 150mg placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Upto 4 years
Secondary outcome [2] 0 0
Time From Randomisation to Second Progression (PFS2)
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Time From Randomisation to Second Subsequent Therapy or Death (TSST)
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Time From Randomisation to First Subsequent Therapy or Death (TFST)
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Time From Randomisation to Study Treatment Discontinuation or Death (TDT)
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1
Timepoint [7] 0 0
At 16 weeks
Secondary outcome [8] 0 0
Adjusted Mean Change From Baseline up to 6 Months in Global Quality of Life (QoL) Score From the EORTC-QLQ-C30 Questionnaire
Timepoint [8] 0 0
From baseline up to 6 months
Secondary outcome [9] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [9] 0 0
Up to 4 years

Eligibility
Key inclusion criteria
Key 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.

Major
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/01/2023
Sample size
Target
Accrual to date
Final
154
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Campbelltown
Recruitment hospital [2] 0 0
Research Site - Randwick
Recruitment hospital [3] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerpen
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussel
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Canada
State/province [20] 0 0
Toronto
Country [21] 0 0
France
State/province [21] 0 0
Amiens
Country [22] 0 0
France
State/province [22] 0 0
Besançon
Country [23] 0 0
France
State/province [23] 0 0
Bordeaux
Country [24] 0 0
France
State/province [24] 0 0
Brest Cedex
Country [25] 0 0
France
State/province [25] 0 0
Clichy Cedex
Country [26] 0 0
France
State/province [26] 0 0
La Roche sur Yon
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Lyon Cedex 03
Country [29] 0 0
France
State/province [29] 0 0
Nice
Country [30] 0 0
France
State/province [30] 0 0
Paris CEDEX 14
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Poitiers
Country [33] 0 0
France
State/province [33] 0 0
STRASBOURG Cedex
Country [34] 0 0
France
State/province [34] 0 0
Toulouse
Country [35] 0 0
France
State/province [35] 0 0
Villejuif
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Germany
State/province [37] 0 0
Bochum
Country [38] 0 0
Germany
State/province [38] 0 0
Bonn
Country [39] 0 0
Germany
State/province [39] 0 0
Dresden
Country [40] 0 0
Germany
State/province [40] 0 0
Frankfurt am Main
Country [41] 0 0
Germany
State/province [41] 0 0
Hamburg
Country [42] 0 0
Germany
State/province [42] 0 0
Hannover
Country [43] 0 0
Germany
State/province [43] 0 0
Leipzig
Country [44] 0 0
Germany
State/province [44] 0 0
München
Country [45] 0 0
Germany
State/province [45] 0 0
Schweinfurt
Country [46] 0 0
Germany
State/province [46] 0 0
Ulm
Country [47] 0 0
Israel
State/province [47] 0 0
Beer Sheva
Country [48] 0 0
Israel
State/province [48] 0 0
Haifa
Country [49] 0 0
Israel
State/province [49] 0 0
Holon
Country [50] 0 0
Israel
State/province [50] 0 0
Nahariya
Country [51] 0 0
Israel
State/province [51] 0 0
Petah Tikva
Country [52] 0 0
Israel
State/province [52] 0 0
Ramat Gan
Country [53] 0 0
Israel
State/province [53] 0 0
Rehovot
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Israel
State/province [55] 0 0
Zefir
Country [56] 0 0
Italy
State/province [56] 0 0
Bologna
Country [57] 0 0
Italy
State/province [57] 0 0
Milano
Country [58] 0 0
Italy
State/province [58] 0 0
Padova
Country [59] 0 0
Italy
State/province [59] 0 0
Parma
Country [60] 0 0
Italy
State/province [60] 0 0
Pescara
Country [61] 0 0
Italy
State/province [61] 0 0
Roma
Country [62] 0 0
Italy
State/province [62] 0 0
San Giovanni Rotondo
Country [63] 0 0
Italy
State/province [63] 0 0
Verona
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Seongnam-si
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Seoul
Country [66] 0 0
Netherlands
State/province [66] 0 0
Amsterdam
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Girona
Country [69] 0 0
Spain
State/province [69] 0 0
L'Hospitalet de Llobregat
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Málaga
Country [72] 0 0
Spain
State/province [72] 0 0
Pamplona
Country [73] 0 0
Spain
State/province [73] 0 0
Sabadell
Country [74] 0 0
Spain
State/province [74] 0 0
Santiago de Compostela
Country [75] 0 0
Spain
State/province [75] 0 0
Valencia
Country [76] 0 0
Spain
State/province [76] 0 0
Zaragoza
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Edinburgh
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Glasgow
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Liverpool
Country [80] 0 0
United Kingdom
State/province [80] 0 0
London
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Manchester
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Northwood
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Nottingham
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Myriad Genetic Laboratories, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT02184195
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02184195