Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status

A Phase II, Open-Label, Multicenter Trial to Assess the Efficacy and Safety of the PARP Inhibitor, Olaparib, Alone in Previously-Treated Patients With Stage IV, Measurable Colorectal Cancer, Stratified by MSI Status

This study is being carried out to see if the new drug, olaparib (AZD2281), can effectively and safely treat advanced large bowel cancer. The primary goal of this clinical trial is to determine whether olaparib will have a beneficial effect on the patient's cancer by causing a response and increasing the time it takes for the cancer to progress.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: olaparib

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
      • Research Site
    • Palm Springs, California, United States
      • Research Site
  • Colorado
    • Aurora, Colorado, United States
      • Research Site
  • Delaware
    • Newark, Delaware, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States
      • Research Site
  • Washington
    • Seattle, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients will have measurable disseminated colorectal cancer that is incurable by surgery
• Patients will have had tumor progression following standard combination front-line or second-line chemotherapy.
• CRC patients who have relapsed or recurrent disease within six months after completing adjuvant or neoadjuvant chemotherapy

Exclusion Criteria:

• Previous treatment with PARP inhibitors, including olaparib.
• Patients with symptomatic, uncontrolled brain metastases.
• Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 4 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used).
• Patients who are unable to swallow orally administered medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MSI - H arm	Drug: olaparib; 400 mg po bid continuously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour Response	Tumour response is the number of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1)	From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit.	From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 months
Overall Survival	Overall survival is defined as the duration from first dose till death from any cause. In absence of death, the time is calculated from first dose till the date subject last known to be alive	Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed up to 35 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Jane Robertson, BSc, MBCHB, MD, AstraZeneca; Principal Investigator: Lawrence P Leichman, MD, Aptium Oncology Gastrointestinal Cancer Consortium; Principal Investigator: Bert H O'Neil, MD, Aptium Oncology Gastrointestinal Cancer Consortium

Publications and helpful links

Helpful Links

• CSR_Synopsis_D9010C00008

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: June 2, 2009
• First Posted (Estimate): June 3, 2009

Study Record Updates

• Last Update Posted (Estimate): November 9, 2016
• Last Update Submitted That Met QC Criteria: September 22, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Colorectal cancer; Olaparib; Stage IV; MSI status; Measurable Colorectal Cancer; Stratified by MSI Status
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: D9010C00008; AGICC 09CRC01