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

NCT ID: NCT02340611

Last Updated: 2018-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2018-06-30

Brief Summary

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.

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Olaparib

Intervention Type: DRUG

Polyadenosine 5'diphosphoribose polymerase (PARP) Inhibitor

Cediranib

Intervention Type: DRUG

Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor that is a potent inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3)

Interventions

Olaparib

Polyadenosine 5'diphosphoribose polymerase (PARP) Inhibitor

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

AZD2281; KU-0059436; AZD2171; Recentin™

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Oza, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

e-Volve

Identifier Type: -

Identifier Source: org_study_id