Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy (POLO)
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|ClinicalTrials.gov Identifier: NCT02184195|
Recruitment Status : Active, not recruiting
First Posted : July 9, 2014
Results First Posted : January 27, 2020
Last Update Posted : March 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Germline BRCA1/2 Mutations and Metastatic Adenocarcinoma of the Pancreas||Drug: Olaparib Drug: Placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||154 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official 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|
|Actual Study Start Date :||December 16, 2014|
|Actual Primary Completion Date :||January 15, 2019|
|Estimated Study Completion Date :||February 26, 2021|
Olaparib tablets po. 300 mg twice daily
Placebo Comparator: Placebo
Placebo tablets twice daily
Match Olaparib 100mg placebo
Match Olaparib 150mg placebo
- 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 ]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.
- Overall Survival (OS) [ Time Frame: Upto 4 years ]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.
- Time From Randomisation to Second Progression (PFS2) [ Time Frame: Up to 4 years ]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.
- Time From Randomisation to Second Subsequent Therapy or Death (TSST) [ Time Frame: Up to 4 years ]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.
- Time From Randomisation to First Subsequent Therapy or Death (TFST) [ Time Frame: Up to 4 years ]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.
- Time From Randomisation to Study Treatment Discontinuation or Death (TDT) [ Time Frame: Up to 4 years ]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.
- Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1 [ Time Frame: Up to 4 years ]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.
- Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1 [ Time Frame: At 16 weeks ]Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
- 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 ]
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.
- Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 4 years ]To assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02184195