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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Mean Objective Response Rate (ORR) by Independent Central Review (ICR) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •History of stroke or transient ischemic attack within 6 months
- •Uncontrolled intercurrent illness
- •Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
- •No prior allogenic bone marrow transplant or double umbilical cord blood transplantation
- •Known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection on antiviral treatment
- •Concomitant use of known strong or moderate CYP3A inhibitors
- •Concomitant use of known strong or moderate CYP3A inducers
研究组 & 干预措施
combination of cediranib and olaparib
Open label
干预措施: cediranib and olaparib (Drug)
结局指标
主要结局
Mean Objective Response Rate (ORR) by Independent Central Review (ICR) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: 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.
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.
次要结局
- 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).)
- Median Overall Survival (OS)(From baseline until death due to any cause, assessed until primary analysis DCO (8 months after last patient received their first dose of IPs).)
- Best Observed Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 Scales(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.)
- Best Observed Change From Baseline in EORTC QLQ-OV28(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.)