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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Olaparib
* Drug: Cediranib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cediranib and Olaparib<br>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<br>* Polyadenosine 5'diphosphoribose polymerase (PARP) Inhibitor<br>* Other names: KU-0059436;Drug: Cediranib<br>* Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor that is a potent inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3)<br>* Other names: Recentin™;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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