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A Study of Cediranib and Olaparib at Disease Worsening in Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02681237
Recruitment Status : Active, not recruiting
First Posted : February 12, 2016
Last Update Posted : September 16, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE February 10, 2016
First Posted Date  ICMJE February 12, 2016
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE April 29, 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2016)
  • Objective Response Rate [ Time Frame: 8 weeks ]
  • Progression-Free Survival Rate [ Time Frame: 16 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2016)
  • CA125 response rate [ Time Frame: 2 years ]
  • Disease control rate [ Time Frame: 2 years ]
  • Overall survival rate [ Time Frame: 2 years ]
  • Number of Adverse Events Experienced [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Cediranib and Olaparib at Disease Worsening in Ovarian Cancer
Official Title  ICMJE A Proof of Concept, Multi-centre, Clinical Trial of the Combination Cediranib-Olaparib at the Time of Disease Progression on PARP Inhibitor in Ovarian Cancer
Brief Summary

This is a proof of concept study (a study to initially assess the benefit a new drug indication) of the combination of two investigational drugs cediranib and olaparib in patients with ovarian cancer whose cancer worsened despite previously receiving a poly (ADP-ribose) polymerase (PARP) inhibitor (such as olaparib).

The purpose of this study is to find out whether taking cediranib and olaparib at the same time will be able to stop tumors from growing further or shrink it.

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 a 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 thought to 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Cediranib
    Small-molecule inhibitor of several tyrosine kinases including VEGFR-1, VEGFR-2, VEGFR-3 and c-kit.
  • Drug: Olaparib
    Poly (ADP-ribose) polymerase (PARP) inhibitor.
Study Arms  ICMJE Experimental: Cediranib and Olaparib

Cediranib will be given by mouth, at a dose of 20 mg, once a day, everyday.

Olaparib will given by mouth, at a dose of 300 mg, twice a day, every day.

Interventions:
  • Drug: Cediranib
  • Drug: Olaparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 9, 2019)
34
Original Estimated Enrollment  ICMJE
 (submitted: February 10, 2016)
30
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age >= 18 years.
  • Performance status <= 2.
  • Histologically confirmed ovarian cancer, high grade serous or high grade endometrioid histology subtype.
  • Radiographically documented disease progression within 28 days of registration and evaluable.
  • Radiological progression on any PARP inhibitor therapy (example: olaparib):

    • a cohort of platinum sensitive recurrence and response for at least 6 months on PARP inhibitor treatment
    • a cohort of platinum resistance with disease progression within 6 months after the last dose of a platinum based chemotherapy
  • Patients who discontinue PARP therapy will be eligible after a break in therapy or intervening therapy.
  • Patients must have adequate bone marrow, renal and hepatic function per local laboratory reference range.
  • Ongoing prior toxicities related to previous treatments must be recovered to <= grade 2 at the time of registration.
  • Left ventricular ejection fraction (LVEF) >= 50% by echocardiograms or multigated acquisition (MUGA) scan within 28 days of registration.
  • Acceptable urine dipstick/urine analysis for proteinuria.
  • Patients are willing to undergo tumour biopsy pre-treatment if a biopsy at the time of progression on olaparib is not available.
  • Life expectancy of greater than 3 months.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patient's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Patients of child bearing potential and their partners who are sexually active must agree to the use of 2 highly effective forms of contraception throughout their participation during the study treatment and for 3 months after last dose of study treatment(s).

Exclusion Criteria:

  • Patients with current bowel obstruction.
  • Patients with known brain metastases.
  • Unacceptable mean corrected QT (QTc) in screening electrocardiograms within 7 days of registration 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.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or cediranib.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Patients with 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.
  • Patients who require maximal doses of calcium channel blockers to stabilize blood pressure.
  • Patients with significant hemorrhage or haemoptysis.
  • Patients who have had recent (within 2 weeks of registration, or until any wound has completely healed) major thoracic or abdominal surgery prior to study start, or a surgical incision that is not fully healed.
  • History of stroke or transient ischemic attack within six months.
  • Patients that are receiving and cannot stop the following prohibited medications prior to Cycle 1, Day 1.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02681237
Other Study ID Numbers  ICMJE e-Volve 1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Amit Oza, M.D. Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP