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

Metastatic Adenocarcinoma of the Pancreas Clinical Trial

— POLO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02184195
• Other study ID #: D081FC00001
• Secondary ID: 2014-001589-85
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2014
• Est. completion date: January 27, 2023

Study information

• Verified date: June 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: January 27, 2023
• Est. primary completion date: January 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Germline BRCA1/2 Mutations and
• Metastatic Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms

Intervention

Drug:
• Olaparib
Tablet -100mg
• Olaparib
Tablet-150mg
• Placebo
Match Olaparib 100mg placebo
• Placebo
Match Olaparib 150mg placebo

Locations

Country	Name	City	State
Australia	Research Site	Campbelltown
Australia	Research Site	Randwick
Australia	Research Site	St Leonards
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brussel
Belgium	Research Site	Leuven
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto
France	Research Site	Amiens
France	Research Site	Besançon
France	Research Site	Bordeaux
France	Research Site	Brest Cedex
France	Research Site	Clichy Cedex
France	Research Site	La Roche sur Yon
France	Research Site	Lille
France	Research Site	Lyon Cedex 03
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Paris CEDEX 14
France	Research Site	Poitiers
France	Research Site	STRASBOURG Cedex
France	Research Site	Toulouse
France	Research Site	Villejuif
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Bonn
Germany	Research Site	Dresden
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	München
Germany	Research Site	Schweinfurt
Germany	Research Site	Ulm
Israel	Research Site	Beer Sheva
Israel	Research Site	Haifa
Israel	Research Site	Holon
Israel	Research Site	Nahariya
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Israel	Research Site	Zefir
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Pescara
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	San Giovanni Rotondo
Italy	Research Site	Verona
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Amsterdam
Spain	Research Site	Barcelona
Spain	Research Site	Girona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Pamplona
Spain	Research Site	Sabadell
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Surrey
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Commack	New York
United States	Research Site	Gilbert	Arizona
United States	Research Site	Houston	Texas
United States	Research Site	Miami	Florida
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Seattle	Washington
United States	Research Site	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	Merck Sharp & Dohme LLC, Myriad Genetic Laboratories, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Up to 4 years
Secondary	Overall Survival (OS)	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.	Upto 4 years
Secondary	Time From Randomisation to Second Progression (PFS2)	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.	Up to 4 years
Secondary	Time From Randomisation to Second Subsequent Therapy or Death (TSST)	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.	Up to 4 years
Secondary	Time From Randomisation to First Subsequent Therapy or Death (TFST)	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.	Up to 4 years
Secondary	Time From Randomisation to Study Treatment Discontinuation or Death (TDT)	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.	Up to 4 years
Secondary	Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1	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.	Up to 4 years
Secondary	Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1	Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.	At 16 weeks
Secondary	Adjusted Mean Change From Baseline up to 6 Months in Global Quality of Life (QoL) Score From the EORTC-QLQ-C30 Questionnaire	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.	From baseline up to 6 months
Secondary	Number of Participants With Adverse Events (AEs)	To assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events	Up to 4 years

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