NCT02184195 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2023-09-13

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

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Time From Randomisation to Second Progression (PFS2)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1

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outcome · POSTED

Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1

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outcome · POSTED

Adjusted Mean Change From Baseline up to 6 Months in Global Quality of Life (QoL) Score From the EORTC-QLQ-C30 Questionnaire

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outcome · POSTED

Number of Participants With Adverse Events (AEs)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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 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
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Olaparib tablets po. 300 mg twice daily
intervention Names
Drug: Olaparib
label
Olaparib
type
EXPERIMENTAL
description
Placebo tablets twice daily
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Olaparib
description
Tablet -100mg
name
Olaparib
type
DRUG
arm Group Labels
Olaparib
description
Tablet-150mg
name
Olaparib
type
DRUG
arm Group Labels
Placebo
description
Match Olaparib 100mg placebo
name
Placebo
type
DRUG
arm Group Labels
Placebo
description
Match Olaparib 150mg placebo
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 154
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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)
time Frame
Up to 4 years

secondary Outcomes

description
To determine the efficacy by assessment of OS of olaparib maintenance monotherapy compared to placebo. The OS was defined as the time from the date of randomization until death due to any cause.
measure
Overall Survival (OS)
time Frame
Upto 4 years
description
To determine efficacy by assessment of PFS2 of olaparib maintenance monotherapy compared to placebo. The PFS2 was defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or death.
measure
Time From Randomisation to Second Progression (PFS2)
time Frame
Up to 4 years
description
To determine the efficacy by assessment of TSST of olaparib maintenance monotherapy compared to placebo. The TSST was defined as time to second subsequent therapy or death.
measure
Time From Randomisation to Second Subsequent Therapy or Death (TSST)
time Frame
Up to 4 years
description
To determine the efficacy by assessment of TFST of olaparib maintenance monotherapy compared to placebo. The TFST was defined as time to first subsequent therapy or death.
measure
Time From Randomisation to First Subsequent Therapy or Death (TFST)
time Frame
Up to 4 years
description
To determine the efficacy by assessment of TDT compared to placebo. compared to placebo. The TDT was defined as time to study treatment discontinuation or death.
measure
Time From Randomisation to Study Treatment Discontinuation or Death (TDT)
time Frame
Up to 4 years
description
To determine efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo. The ORR is defined as the number of with a BoR of CR and PR according to the BICR data divided by the number of patients in the treatment group with measurable disease at baseline.
measure
Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1
time Frame
Up to 4 years
description
Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
measure
Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1
time Frame
At 16 weeks
description
To assess the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale. The EORTC-QLQ-C30 is defined as EORTC QLQ-C30: a questionnaire (30 questions) used to evaluate disease symptoms, functional impacts (eg, physical functioning), and HRQoL and to characterize clinical benefit from the patient perspective. The HRQoL score ranges from 0 to 100. A higher score indicates better QoL. A score change of 10 points was pre-defined as clinically meaningful. bd twice daily.
measure
Adjusted Mean Change From Baseline up to 6 Months in Global Quality of Life (QoL) Score From the EORTC-QLQ-C30 Questionnaire
time Frame
From baseline up to 6 months
description
To assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
measure
Number of Participants With Adverse Events (AEs)
time Frame
Up to 4 years

Full study description

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
detailed Description: 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.

Source references

references

citation
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
31157963
type
BACKGROUND
citation
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.
pmid
35834777
type
DERIVED
citation
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.
pmid
35596182
type
DERIVED
citation
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pmid
33959007
type
DERIVED
citation
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.
pmid
33364840
type
DERIVED
citation
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.
pmid
32073954
type
DERIVED
citation
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.
pmid
31562758
type
DERIVED
citation
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.
pmid
29223478
type
DERIVED