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Trial record 2 of 2 for:    olaparib | Pancreatic cancer | United Kingdom

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02184195
Recruitment Status : Active, not recruiting
First Posted : July 9, 2014
Results First Posted : January 27, 2020
Last Update Posted : July 17, 2020
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE June 6, 2014
First Posted Date  ICMJE July 9, 2014
Results First Submitted Date  ICMJE January 14, 2020
Results First Posted Date  ICMJE January 27, 2020
Last Update Posted Date July 17, 2020
Actual Study Start Date  ICMJE December 16, 2014
Actual Primary Completion Date January 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 3, 2014)
Progression free survival (PFS) by central review of modified RECIST 1.1 [ Time Frame: Up to 4 years ]
Efficacy by assessment of PFS (time from randomisation to objective disease progression according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) or death) of olaparib maintenance monotherapy compared to placebo, using blinded independent central review (BICR) of radiological scans.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2020)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2014)
  • Overall Survival (OS) [ Time Frame: Up to 4 years ]
    Efficacy by assessment of OS (time from randomisation to death by any cause) of olaparib maintenance monotherapy compared to placebo
  • Time from randomisation to second progression or death (PFS2) [ Time Frame: Up to 4 years ]
    Efficacy by assessment of PFS2 (time from randomisation to second progression, defined as objective radiological or symptomatic progression, or death) of olaparib maintenance monotherapy compared to placebo.
  • Time From Randomisation to First Subsequent Therapy or Death (TFST) [ Time Frame: Up to 4 years ]
    Efficacy by assessment of TFST (time from randomisation to the earlier of first subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
  • Time From Randomisation to Second Subsequent Therapy or Death (TSST) [ Time Frame: Up to 4 years ]
    Efficacy by assessment of TSST (time from randomisation to the earlier of second subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
  • Time From Randomisation to Study Treatment Discontinuation or Death (TDT) [ Time Frame: Up to 4 years ]
    Efficacy by assessment of TDT (time from randomisation to the earlier of study treatment discontinuation or death) of olaparib maintenance monotherapy compared to placebo. compared to placebo.
  • Objective response rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years. ]
    Efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo
  • Disease control rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years ]
    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 in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [ Time Frame: Up to 4 years ]
    Assessment of the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale
  • Safety and tolerability of olaparib [ Time Frame: Up to 4 years ]
    Assessment of adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry and haematology.
  • Time to deterioration of global quality of life (QoL) [ Time Frame: Up to 4 years. ]
    Assessment of the effect of olaparib on time to deterioration of global health status/QoL and pancreatic pain as measured by the EORTC-QLQ-C30 global QoL scale and the PAN-26 pancreatic pain scale.
  • Improvement rate of global quality of life (QoL) [ Time Frame: Up to 4 years ]
    Assessment of the effect of olaparib on improvement rate of global health status/QoL and pancreatic pain as measured by the EORTC-QLQ-C30 global QoL scale and the PAN-26 pancreatic pain scale.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Germline BRCA1/2 Mutations and
  • Metastatic Adenocarcinoma of the Pancreas
Intervention  ICMJE
  • Drug: Olaparib
    Tablet -100mg
  • Drug: Olaparib
    Tablet-150mg
  • Drug: Placebo
    Match Olaparib 100mg placebo
  • Drug: Placebo
    Match Olaparib 150mg placebo
Study Arms  ICMJE
  • Experimental: Olaparib
    Olaparib tablets po. 300 mg twice daily
    Interventions:
    • Drug: Olaparib
    • Drug: Olaparib
  • Placebo Comparator: Placebo
    Placebo tablets twice daily
    Interventions:
    • Drug: Placebo
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 14, 2020)
154
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2014)
145
Estimated Study Completion Date  ICMJE February 26, 2021
Actual Primary Completion Date January 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Korea, Republic of,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02184195
Other Study ID Numbers  ICMJE D081FC00001
2014-001589-85 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • Myriad Genetic Laboratories, Inc.
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP