Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer

NCT02889900 | Completed Phase 2 Results

• 1 other identifier: D8488C00001
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 25

Brief Summary

This is an open label, single arm, multi-center study to assess the efficacy and safety of the combination of cediranib and olaparib tablets in platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma patients who have received at least 3 prior lines of chemotherapy and who do not carry deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutations.

Conditions

Recurrent Platinum Resistant Ovarian Cancer

Keywords

ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Mean Objective Response Rate (ORR) by Independent Central Review (ICR) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  The ORR was defined as the percentage of patients with objective response (complete response \[CR\] or partial response \[PR\]) according to RECIST 1.1 and was assessed by ICR. Only patients whose CR/PR response was confirmed by a second scan at least 4 weeks after the initial response, with no evidence of progression between the initial and CR/PR confirmation visit were included. CR: Disappearance of all target lesions (TLs) and non-TLs (NTLS) since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 millimeters (mm). PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters. Data obtained up until progression, or last evaluable assessment in the absence of progression were included in the assessment of ORR.

  From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Secondary Outcomes (8)

• ORR by Investigator Assessment Using RECIST 1.1

  From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

• Median Duration of Response (DoR) by ICR and Investigator Assessment Using RECIST 1.1

  From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

• Disease Control Rate (DCR) by ICR and Investigator Assessment Using RECIST 1.1

  From baseline up to 6 months after first doses of IPs. RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

• Median PFS by ICR and Investigator Assessment Using RECIST 1.1

  From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

• Median Time to Treatment Discontinuation or Death (TDT)

  From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs).

Study Arms (1)

combination of cediranib and olaparib

EXPERIMENTAL

Open label

Drug: cediranib and olaparib

Interventions

cediranib and olaparib DRUG

Cediranib tablets oral dose 30 mg once daily; Olaparib(Lynparza) tablet 200 mg twice daily Dose reduction for both products is allowed

Also known as: Olaparib: also known as Lynparza

combination of cediranib and olaparib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness to provide written informed consent, and to comply with the requirements of the protocol
• Females aged ≥18 years with previous histologically proven diagnosis of high grade serous, high grade endometroid or clear cell ovarian cancer, fallopian tube or primary peritoneal carcinoma
• No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes
• Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy
• CT/MRI evidence of measurable disease as per RECIST 1.1 defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) and which is suitable for accurate repeated measurements
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy ≥12 weeks
• Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
• At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol
• Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided
• Patients must have adequate organ and bone marrow function
• Adequately controlled blood pressure
• Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
• Able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of IPs

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous enrollment in the present study.
• Exposure to any IP during the last 4 weeks prior to enrollment.
• Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi
• Recent cancer-directed therapies: Radiotherapy (RT) within 4 weeks, chemotherapy or other systemic anti-cancer therapy within 4 weeks, or prior anti-angiogenic treatment (e.g., bevacizumab) within 6 weeks prior to starting treatment
• Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease
• Major surgical procedure within 2 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
• Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
• History of intra-abdominal abscess within 3 months prior to starting treatment
• History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula
• Other malignancy within the last 5 years
• Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
• Central nervous system metastases
• Patients with any of the following: History of myocardial infarction within 6 months prior to starting treatment; Unstable angina; Resting electrocardiogram (ECG) with clinically significant abnormal findings; New York Heart Association functional classification of III or IV
• Left ventricular ejection fraction (LVEF) \< lower limit of normal (LLN) per institutional guidelines, or \<55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors: Prior treatment with anthracyclines; Prior treatment with trastuzumab; Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT; History of myocardial infarction within 6-12 months prior to start of IPs; Prior history of other significant impaired cardiac function

Sponsors & Collaborators

• AstraZeneca: lead
• Myriad Genetic Laboratories, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (25)

Research Site

Mobile, Alabama, 36604, United States

Location

Research Site

Anchorage, Alaska, 99508, United States

Location

Research Site

Downey, California, 90241, United States

Location

Research Site

Greenbrae, California, 94904, United States

Location

Research Site

Orange, California, 92868, United States

Location

Research Site

San Diego, California, 92123, United States

Location

Research Site

San Francisco, California, 94115, United States

Location

Research Site

West Hollywood, California, 90048, United States

Location

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Miami, Florida, 33176, United States

Location

Research Site

Orlando, Florida, 32804, United States

Location

Research Site

Augusta, Georgia, 30901, United States

Location

Research Site

Newnan, Georgia, 30265, United States

Location

Research Site

Fort Wayne, Indiana, 46804, United States

Location

Research Site

Westwood, Kansas, 66205, United States

Location

Research Site

Covington, Louisiana, 70433, United States

Location

Research Site

Towson, Maryland, 21204, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Billings, Montana, 59101, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

Rochester, New York, 14642, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Winston-Salem, North Carolina, 27103, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Seattle, Washington, 98104, United States

Location

Related Links

• CSR synopsis

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazenca.com

1-877-240-9479

Study Officials

• Jung-Min Lee, M.D.

  NIH - National Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: September 7, 2016
• Study Start: January 17, 2017
• Primary Completion: August 27, 2019
• Study Completion: March 16, 2021
• Last Updated: March 8, 2022
• Results First Posted: August 20, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (25)