Clinical trial NCT02340611: A Study of Cediranib and Olaparib at the Time Ovarian Cancer Worsens on Olaparib
Official title: A Proof of Concept Clinical Trial of the Combination Cediranib-Olaparib at the Time of Disease Progression on Olaparib in Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2015-01-16
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of patients whose cancer shrinks or disappears after treatment
timeFrame: 2 years
Secondary outcomes:
measure: Percentage of decrease in CA-125 levels after treatment
timeFrame: 2 years
measure: Mutation status of genes compared to response to treatment
timeFrame: 2 years
measure: Number of occurences per side effect and severity
timeFrame: 2 years
measure: Assess patient reported outcomes during treatment
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Amit Oza, M.D.
role: PRINCIPAL_INVESTIGATOR
References: