A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have Not Progressed After First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 940
- 试验地点
- 1
- 主要终点
- Investigator-assessed Progression-free Survival (PFS)
研究概览
简要总结
This was a study to determine whether therapy with pazopanib was effective and safe in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose cancer had not progressed on first line chemotherapy.
详细描述
This was a randomized, two-arm, placebo controlled, double-blind, multicenter, intergroup Phase III study in women with non-bulky FIGO (International Federation of Gynecology and Obstetrics) Stage II - IV ovarian, fallopian tube, or primary peritoneal cancer that had not progressed (i.e., complete response (CR), partial response (PR), stable disease (SD) after completing their first-line chemotherapy for advanced ovarian cancer. Approximately 900 subjects were to be enrolled into the study. Study was closed following 3rd overall survival (OS) interim analysis as planned per protocol, which confirmed futility.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •written informed consent
- •At least 18 years old.
- •Histologically confirmed, FIGO stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy.
- •Study randomization at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved.
- •No evidence of disease progression
- •ECOG status of 0 or 2
- •Able to swallow and retain oral medication.
- •Adequate hematologic, hepatic, and renal system function as follows:
- •Hematologic
- •Absolute neutrophil count (ANC) at least 1.5 X 10^9/L
- •Hemoglobin at least 9 g/dL (or 5.59 mmol/L)
- •Platelets at least 100 X 10^9/L
- •Prothrombin time (PT) or international normalized ratio (INR) up to 1.2 X ULN
- •Activated partial thromboplastin time (aPTT) up to 1.2 X ULN Hepatic
- •Total bilirubin up to 1.5 X ULN
- •AST and ALT up to 2.5 X ULN Renal
- •Serum creatinine up to 1.5 mg/dL
- •Or, if greater than 1.5 mg/dL:
- •Calculated creatinine clearance at least 50 mL/min Urine Protein
- •Urine protein is 0, trace, or +1 determined by dipstick urinalysis, or < 1.0 gram determined by 24- hour urine protein analysis.
- •Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception.
排除标准
- •Either (a) bulky disease, or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
- •Synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless certain conditions are met.
- •Clinically significant gastrointestinal abnormalities
- •Prolongation of corrected QT interval (QTc) > 480 msecs
- •History of any one or more cardiovascular conditions within the past 6 months prior to randomization
- •Cardiac angioplasty or stenting
- •Myocardial infarction
- •Unstable angina
- •Symptomatic peripheral vascular disease
- •Class III or IV congestive heart failure
- •Poorly controlled hypertension
- •History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization
- •Major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
- •Evidence of active bleeding or bleeding diathesis.
- •Hemoptysis within 6 weeks prior to randomization.
- •Endobronchial metastases.
- •Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- •Investigational or anti-VEGF anticancer therapy prior to study randomization.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
- •Invasive malignancies that showed activity of disease within 5 years prior to randomization
研究组 & 干预措施
Placebo
matched placebo tablet administered orally once daily for up to 24 months
干预措施: Placebo (Drug)
Pazopanib
Pazopanib tablet administered orally at 800 mg once daily for up to 24 months
干预措施: Pazopanib (Drug)
结局指标
主要结局
Investigator-assessed Progression-free Survival (PFS)
时间窗: From the date of randomization until the date of progression or death due to any cause (median time of follow-up was 17.9 months for pazopanib and 12.3 months for placebo)
PFS is the interval between the date of randomization and the date of progression, defined by Response Evaluation Criteria in Solid Tumors (RECIST), or death due to any cause. Per RECIST, for target lesions (TLs), disease progression (PD) is defined as \>=20% increase in the sum of the longest diameters (LD) of TLs, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of \>=1 new lesions. For non-target lesions (NTLs), PD is defined as the appearance of \>=1 new lesions and/or unequivocal progression of existing NTLs. Participants (par.) who did not progress/die were censored at the date of last adequate assessment (LAA). Par. who started a new anti-cancer therapy (ACT) prior to radiological progression/death were censored at the date of LAA prior to the new ACT. Par. who progressed/died after an extended period (\>=12 months) without adequate assessment (AA) were censored at the date of their last visit with AA prior to progression/death.
次要结局
- Overall Survival: Number of Participants Experiencing Death(From the date of randomization until the date of death due to any cause up to approximately 25 months)
- Overall Survival - Median(From the date of randomization until the date of death due to any cause up to approximately 25 months)
- Change From Baseline in QLQ-OV-28 Module Attitude to Disease/Treatment Functional Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- 3-year Progression-free Survival(Up to 3 years after randomization)
- Change From Baseline in QLQ-OV-28 Module Body Image Functional Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Change From Baseline in QLQ-OV-28 Module Sexuality Functional on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Progression-free Survival Per Gynecologic Cancer Intergroup (GCIG) Criteria(From the date of randomization until the date of progression per GCIG criteria or death due to any cause (median time of follow-up was 16.8 months for pazopanib and 11.9 months for placebo))
- Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Change From Baseline in QLQ-OV-28 Module Other Chemotherapy Side Effects (SE) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Change From Baseline in the EuroQOL EQ-5D (Five Dimensions) Thermometer Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Number of Participants With the Indicated Treatment-emergent Thyroid-stimulating Hormone (TSH) Elevations Above 5 Million Units Per Liter (MU/L)(From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo))
- Change From Baseline in QLQ-OV-28 Module Peripheral Neuropathy (PN) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Change From Baseline in QLQ-OV-28 Module Hormonal/Menopausal Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Change From Baseline in the EQ-5D (Five Dimensions) Utility Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Number of Participants With the Indicated Grade 2, 3, and 4 On-therapy Adverse Events Occurring in >=10% of Participants in Either Treatment Arm(From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo))
- Number of Participants With the Indicated On-therapy Chemistry Grade Shifts From Baseline Grade(From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo))
- Change From Baseline in QLQ-OV-28 Module Abdominal (AB)/Gastrointestinal (GI) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25(Baseline; Week 13; Months 7, 10, 13, 16, and 25)
- Number of Participants With the Indicated On-therapy Hematology Grade Shifts From Baseline Grade(From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo))