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

• ClinicalTrials.gov Identifier: NCT02340611
• Recruitment Status: Completed
• First Posted: January 16, 2015
• Last Update Posted: June 12, 2018
• Sponsor: University Health Network, Toronto
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): University Health Network, Toronto

Tracking Information

• First Submitted Date: January 13, 2015
• First Posted Date: January 16, 2015
• Last Update Posted Date: June 12, 2018
• Study Start Date: June 2015
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 13, 2015): Percentage of patients whose cancer shrinks or disappears after treatment [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 13, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• 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™

Study Arms

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.

Interventions:

• Drug: Olaparib
• Drug: Cediranib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 30, 2017): 4
• Original Estimated Enrollment (submitted: January 13, 2015): 5
• Actual Study Completion Date: June 2018
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02340611
• Other Study ID Numbers: e-Volve
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University Health Network, Toronto
• Study Sponsor: University Health Network, Toronto
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: Amit Oza, M.D.; Princess Margaret Cancer Centre

• PRS Account: University Health Network, Toronto
• Verification Date: June 2018