A Study of Cediranib and Olaparib at Disease Worsening in Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT02681237|
Recruitment Status : Completed
First Posted : February 12, 2016
Last Update Posted : May 9, 2022
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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.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer||Drug: Cediranib Drug: Olaparib||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||April 29, 2016|
|Actual Primary Completion Date :||January 10, 2022|
|Actual Study Completion Date :||March 25, 2022|
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.
Small-molecule inhibitor of several tyrosine kinases including VEGFR-1, VEGFR-2, VEGFR-3 and c-kit.
Poly (ADP-ribose) polymerase (PARP) inhibitor.
- Objective Response Rate [ Time Frame: 8 weeks ]objective response rate by RECIST 1.1
- Progression-Free Survival Rate [ Time Frame: 16 weeks ]objective response rate by RECIST 1.1 or death
- CA125 response rate [ Time Frame: 2 years ]objective response rate by GCIG criteria
- Disease control rate [ Time Frame: 2 years ]
- Overall survival rate [ Time Frame: 2 years ]
- Number of Adverse Events Experienced [ Time Frame: 2 years ]
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02681237
|Princess Margaret Cancer Centre|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Amit Oza, M.D.||Princess Margaret Cancer Centre|
|Responsible Party:||University Health Network, Toronto|
|Other Study ID Numbers:||
|First Posted:||February 12, 2016 Key Record Dates|
|Last Update Posted:||May 9, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Female
Endocrine System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Poly(ADP-ribose) Polymerase Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors