Clinical trial NCT02889900: Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer
Official title: A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Platinum Resistant Ovarian Cancer
Keywords: ovarian cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Myriad Genetic Laboratories, Inc.
name: Merck Sharp & Dohme LLC
First posted: 2016-09-07
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The study will recruit approximately 60 patients aged ≥18 years, with histologically proven diagnosis of platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma who have received at least 3 prior lines of therapy, and who do not carry a deleterious or suspected deleterious germline BRCA mutation. All patients should have recurrent platinum resistant disease. The receipt of prior antiangiogenic treatment (e.g. bevacizumab) is optional. If used, it can be in the first line or recurrent setting. To be eligible to enter the study, all patients should have measurable disease (as assessed by the Investigator).

There is no maximum duration for taking the study treatments (cediranib+olaparib). Patients should continue on study treatments until objective radiological disease progression, as defined by RECIST version 1.1 guidelines, or they meet other discontinuation criteria. Following discontinuation of study treatment patients will be followed for disease progression (if they have not already progressed), survival and post-progression anti cancer therapies until the data cut-off for the primary analysis, approximately 8 months after enrollment of the last patient.

Eligibility criteria: Inclusion Criteria:

1. Ability and willingness to provide written informed consent, and to comply with the requirements of the protocol
2. 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
3. No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes
4. Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy
5. 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
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Life expectancy ≥12 weeks
8. 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.
9. At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol
10. Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided
11. Patients must have adequate organ and bone marrow function
12. Adequately controlled blood pressure
13. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
14. Able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
15. 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

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2. Previous enrollment in the present study.
3. Exposure to any IP during the last 4 weeks prior to enrollment.
4. Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi
5. 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
6. Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease
7. 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
8. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
9. History of intra-abdominal abscess within 3 months prior to starting treatment
10. 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
11. Other malignancy within the last 5 years
12. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
13. Central nervous system metastases
14. 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
15. 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
16. History of stroke or transient ischemic attack within 6 months
17. Uncontrolled intercurrent illness
18. Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
19. No prior allogenic bone marrow transplant or double umbilical cord blood transplantation
20. Known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection on antiviral treatment
21. Concomitant use of known strong or moderate CYP3A inhibitors
22. Concomitant use of known strong or moderate CYP3A inducers

Primary outcomes:
measure: Mean Objective Response Rate (ORR) by Independent Central Review (ICR) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: 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:
measure: ORR by Investigator Assessment Using RECIST 1.1
timeFrame: 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.
measure: Median Duration of Response (DoR) by ICR and Investigator Assessment Using RECIST 1.1
timeFrame: 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.
measure: Disease Control Rate (DCR) by ICR and Investigator Assessment Using RECIST 1.1
timeFrame: 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.
measure: Median PFS by ICR and Investigator Assessment Using RECIST 1.1
timeFrame: 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.
measure: Median Time to Treatment Discontinuation or Death (TDT)
timeFrame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs).
measure: Median Overall Survival (OS)
timeFrame: From baseline until death due to any cause, assessed until primary analysis DCO (8 months after last patient received their first dose of IPs).
measure: Best Observed Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 Scales
timeFrame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). EORTC QLQ-C30 assessments were performed at baseline and every 8 weeks relative to first dose until discontinuation of IPs.
measure: Best Observed Change From Baseline in EORTC QLQ-OV28
timeFrame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). EORTC QLQ-OV28 assessments were performed at baseline and every 8 weeks relative to first dose until discontinuation of IPs.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Anchorage
country: United States
facility: Research Site
state: Alaska
city: Downey
country: United States
facility: Research Site
state: California
city: Greenbrae
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Newnan
country: United States
facility: Research Site
state: Georgia
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Covington
country: United States
facility: Research Site
state: Louisiana
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Billings
country: United States
facility: Research Site
state: Montana
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Seattle
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: NIH - National Cancer Institute
name: Jung-Min Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: