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

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02184195
First Posted: July 9, 2014
Last Update Posted: November 8, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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

Condition Intervention Phase
Germline BRCA1/2 Mutations and Metastatic Adenocarcinoma of the Pancreas Drug: Olaparib Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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.


Estimated Enrollment: 145
Actual Study Start Date: December 16, 2014
Estimated Study Completion Date: July 31, 2019
Estimated Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib
Olaparib tablets po. 300 mg twice daily
Drug: Olaparib
Tablet -100mg
Drug: Olaparib
Tablet-150mg
Placebo Comparator: Placebo
Placebo tablets twice daily
Drug: Placebo
Match Olaparib 100mg placebo
Drug: Placebo
Match Olaparib 150mg placebo

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

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


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 astrazeneca@emergingmed.com

  Show 135 Study Locations
Sponsors and Collaborators
AstraZeneca
Myriad Genetic Laboratories, Inc.
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02184195     History of Changes
Other Study ID Numbers: D081FC00001
2014-001589-85 ( EudraCT Number )
First Submitted: June 6, 2014
First Posted: July 9, 2014
Last Update Posted: November 8, 2017
Last Verified: November 2017

Keywords provided by AstraZeneca:
BRCA, metastatic adenocarcinoma pancreas, maintenance olaparib monotherapy, first line platinum chemotherapy, pancreatic cancer, PARP inhibitor

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents