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

NCT02681237 | Completed DMC

• 1 other identifier: e-Volve 1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  objective response rate by RECIST 1.1

  8 weeks

• Progression-Free Survival Rate

  objective response rate by RECIST 1.1 or death

  16 weeks

Secondary Outcomes (4)

• CA125 response rate

  2 years

• Disease control rate

  2 years

• Overall survival rate

  2 years

• Number of Adverse Events Experienced

  2 years

Study Arms (1)

Cediranib and Olaparib

EXPERIMENTAL

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.

Drug: Cediranib; Drug: Olaparib

Interventions

Cediranib DRUG

Small-molecule inhibitor of several tyrosine kinases including VEGFR-1, VEGFR-2, VEGFR-3 and c-kit.

Cediranib and Olaparib

Olaparib DRUG

Poly (ADP-ribose) polymerase (PARP) inhibitor.

Cediranib and Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• AstraZeneca: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Lheureux S, Oaknin A, Garg S, Bruce JP, Madariaga A, Dhani NC, Bowering V, White J, Accardi S, Tan Q, Braunstein M, Karakasis K, Cirlan I, Pedersen S, Li T, Farinas-Madrid L, Lee YC, Liu ZA, Pugh TJ, Oza AM. EVOLVE: A Multicenter Open-Label Single-Arm Clinical and Translational Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer after PARP Inhibition Progression. Clin Cancer Res. 2020 Aug 15;26(16):4206-4215. doi: 10.1158/1078-0432.CCR-19-4121. Epub 2020 May 22.

  PMID: 32444417 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

cediranib; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Amit Oza, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 12, 2016
• Study Start: April 29, 2016
• Primary Completion: January 10, 2022
• Study Completion: March 25, 2022
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)