A Two-Part, Randomized Phase III, Double-Blind, Multicenter Trial Assessing The Efficacy And Safety of Pertuzumab In Combination With Standard Chemotherapy Vs. Placebo Plus Standard Chemotherapy In Women With Recurrent Platinum-Resistant Epithelial Ovarian Cancer And Low HER3 mRNA Expression
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 68
- 主要终点
- Part 1: Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
This two-part, multicenter study will evaluate the safety, tolerability and efficacy of pertuzumab in combination with standard chemotherapy in women with recurrent platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in, participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized, double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, and/or fallopian tube cancer that is platinum-resistant or refractory
- •Low Human epidermal growth factor receptor (HER) 3 messenger ribonucleic acid (mRNA) expression
- •At least one measurable and/or non-measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 50 percent (%)
- •Negative serum pregnancy test in women of childbearing potential
- •Women of childbearing potential must agree to use effective contraception as defined by protocol during and for at least 6 months post study treatment
排除标准
- •Non-epithelial tumors
- •Ovarian tumors with low malignant potential (borderline tumors)
- •History of other malignancy of prognostic relevance within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma, or tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the breast
- •Previous treatment with more than 2 chemotherapy regimens
- •Any prior radiotherapy to the pelvis or abdomen
- •History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer (uncontrolled seizures), unless adequately treated with standard medical therapy
- •Pre-existing peripheral neuropathy >/= common toxicity criteria (CTC) grade 2 (applicable for paclitaxel cohort only)
- •Inadequate organ function
- •Uncontrolled hypertension or clinically significant cardiovascular disease
- •Current known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV)
- •Current chronic daily treatment with corticosteroids (>/= 10 mg per day of methylprednisolone or equivalent), excluding inhaled steroids
- •History of receiving any investigational treatment within 28 days prior to first study drug administration
- •For Part 2 of the trial: prior enrollment into Part 1 of the trial
- •Concurrent participation in any therapeutic clinical trial
研究组 & 干预措施
Part 1: Pertuzumab + Topotecan
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Paclitaxel (Chemotherapy) (Drug)
Part 1: Pertuzumab + Topotecan
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Pertuzumab (Drug)
Part 1: Pertuzumab + Topotecan
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Topotecan (Chemotherapy) (Drug)
Part 1: Pertuzumab + Paclitaxel
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Paclitaxel (Chemotherapy) (Drug)
Part 1: Pertuzumab + Paclitaxel
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Pertuzumab (Drug)
Part 1: Pertuzumab + Paclitaxel
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
干预措施: Placebo (Drug)
Part 2: Pertuzumab+Chemotherapy
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Pertuzumab (Drug)
Part 2: Pertuzumab+Chemotherapy
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Gemcitabine (Chemotherapy) (Drug)
Part 2: Pertuzumab+Chemotherapy
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Paclitaxel (Chemotherapy) (Drug)
Part 2: Pertuzumab+Chemotherapy
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Topotecan (Chemotherapy) (Drug)
Part 2: Placebo+Chemotherapy
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Gemcitabine (Chemotherapy) (Drug)
Part 2: Placebo+Chemotherapy
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Paclitaxel (Chemotherapy) (Drug)
Part 2: Placebo+Chemotherapy
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Placebo (Drug)
Part 2: Placebo+Chemotherapy
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
干预措施: Topotecan (Chemotherapy) (Drug)
结局指标
主要结局
Part 1: Percentage of Participants With Adverse Events (AEs)
时间窗: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
时间窗: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
次要结局
- Part 2: Overall Survival(Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression))
- Part 1- Objective Response Rate (ORR)(Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression))
- Part 2: Progression-free Survival (PFS) Assessed by the Investigator(Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression))
- Part 2- Objective Response Rate (ORR)(Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression))
- Part 1: PFS Assessed by the Investigator(Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression))
- Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score(Baseline (assessed at baseline and every 9 weeks from randomization until disease progression))
- Part 2: Percentage of Participants With Adverse Events (AEs)(Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment))