A Study of Cediranib and Olaparib at the Time Ovarian Cancer Worsens on Olaparib

June 11, 2018 updated by: University Health Network, Toronto

A Proof of Concept Clinical Trial of the Combination Cediranib-Olaparib at the Time of Disease Progression on Olaparib in Ovarian Cancer

This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful adding investigational drug cediranib to olaparib after disease progression on olaparib alone in patients with ovarian cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cediranib works by blocking (inhibiting) several specific proteins in cancer cells called the vascular endothelial growth factor (VEGF) receptors. These proteins are important in the formation of blood vessels to the tumor. It is believed that many tumors survive because the blood vessels on the tumors bring oxygen and nutrients to the cancer cells which enable them to grow. If the formation of the blood vessels is blocked, the tumor cells may die.

Olaparib works by blocking protein called poly [adenosine diphosphate-ribose] polymerase (PARP). PARP is an important protein which tries to fix damaged deoxyribonucleic acid (DNA, molecules that contain important instructions for the development of cells). Many cancers are though develop from damaged DNA. By blocking PARP from fixing damaged DNA, the tumor cells may die.

Adding cediranib to olaparib, and therefore blocking several different mechanisms for cancer growth, may stop tumor growth.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18 years or older
  • Performance status 2 or less
  • Ovarian cancer, high grade serous or high grade endometrioid histology subtype
  • Radiographically documented disease progression per RECIST 1.1
  • Progression on olaparib therapy after an initial good response (more than 6 months)
  • Patients must have adequate bone marrow, renal and hepatic function per local laboratory reference range
  • Ongoing prior toxicities related to previous treatments recovered to grade 2 or less
  • LVEF>50% by echocardiograms or MUGA
  • Urine dipstick for proteinuria <2+
  • Willing to undergo tumour biopsy pre-treatment
  • Life expectancy of greater than 3 months
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Current bowel obstruction
  • Known brain metastases
  • Mean QTc >470 msec (with Bazett's correction) in screening ECG or history of familial long QT syndrome.
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • A New York Heart Association classification of III or IV requiring concurrent use of drugs or biologics with proarrhythmic potential.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or cediranib
  • Unable to swallow orally administered medication and/or gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Myelodysplastic syndrome/acute myeloid leukaemia
  • Immuno-compromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with known active hepatitis (i.e.,hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cediranib and Olaparib
Cediranib, 20 mg , orally, once a day, every day. Olaparib, 150 mg or 200 mg (depending on previous treatment dose), orally, once a day, every day.
Drug: Olaparib
Polyadenosine 5'diphosphoribose polymerase (PARP) Inhibitor
Other Names:
  • AZD2281
  • KU-0059436
Drug: Cediranib
Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor that is a potent inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3)
Other Names:
  • AZD2171
  • Recentin™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients whose cancer shrinks or disappears after treatment
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of decrease in CA-125 levels after treatment
Time Frame: 2 years
2 years
Mutation status of genes compared to response to treatment
Time Frame: 2 years
2 years
Number of occurences per side effect and severity
Time Frame: 2 years
2 years
Assess patient reported outcomes during treatment
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

June 1, 2018

Study Completion (Actual)

June 1, 2018

Study Registration Dates

First Submitted

January 13, 2015

First Submitted That Met QC Criteria

January 13, 2015

First Posted (Estimate)

January 16, 2015

Study Record Updates

Last Update Posted (Actual)

June 12, 2018

Last Update Submitted That Met QC Criteria

June 11, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • e-Volve

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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