A Multicenter Open-Label Single-Arm Phase II Study Evaluating the Safety and Efficacy of Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Metastatic, Recurrent or Persistent Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 152
- 试验地点
- 43
- 主要终点
- Percentage of Participants with GI Perforation/Fistula Events by Grade According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
研究概览
简要总结
This study is to assess safety as defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula in participants treated with bevacizumab 15 milligrams per kilogram (mg/kg) in combination with paclitaxel and carboplatin, all repeated every 3 weeks, for recurrent, persistent or metastatic cervical cancer. In addition, this study will include evaluation of the overall safety profile of bevacizumab in combination with paclitaxel and carboplatin in this setting, assessment of GI perforation/fistula, GI-vaginal fistula and GU fistula events over time, and evaluation of efficacy.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Life expectancy greater than or equal to (>=3) months
- •For women who are not postmenopausal or surgically sterile, agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 6 months after the last dose of study drug
- •Distant metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy
- •Either measurable or non-measurable disease. If disease is non-measurable or limited to the radiation field, a biopsy or fine-needle aspiration is required to confirm malignancy
- •Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care
- •Adequate hematological, renal and hepatic function
- •Normal blood coagulation parameters
- •Recovered (to Grade less than or equal to [<=] 1) from the effects of prior surgery, radiation therapy or chemoradiotherapy
排除标准
- •Pregnant or lactating
- •History of other malignancy within 5 years before screening, except for non-melanoma skin carcinoma
- •Ongoing disease involving the bladder or rectum at screening/baseline. In participants with pelvic disease, absence of tumor in the bladder or rectal mucosa must be demonstrated by magnetic resonance imaging (MRI) (preferred method, or endoscopy/cystoscopy if MRI is not easily accessible) within 28 days before enrolment
- •Evidence of abdominal free air
- •Bilateral hydronephrosis
- •Untreated central nervous system (CNS) metastases
- •Prior chemotherapy for recurrent, persistent or metastatic cervical cancer. Prior adjuvant or neoadjuvant chemotherapy for Stage I-IVA disease (i.e. for non-metastatic disease) is permitted if completed greater than (>) 6 months before first study dose
- •Prior chemoradiation within the 3 months preceding first study dose
- •Prior radiotherapy delivered using cobalt
- •Prior or current bevacizumab or other anti-angiogenic treatment
- •Requirement for treatment with any medicinal product that contraindicates the use of any of the study drugs, may interfere with the planned treatment, affects participant compliance or puts the participant at high risk for treatment-related complications
- •Treatment with another investigational agent within 28 days or 2 investigational agent half-lives before first study dose
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days before the first dose of bevacizumab or anticipation of the need for major surgery during the course of study treatment
- •Minor surgical procedure within 2 days before the first dose of study drug
- •Any prior history of fistula or GI perforation
- •Known hypersensitivity to bevacizumab or any of its excipients, Chinese hamster ovary cell products or other recombinant human or humanized antibodies to any planned chemotherapy
- •Active GI bleeding or ulcer
- •Uncontrolled hypertension
- •Clinically significant active cardiovascular disease
- •National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, Grade greater than or equal to (>=) 2 peripheral vascular disease
研究组 & 干预措施
Bevacizumab in Combination with Carboplatin and Paclitaxel
Administration of bevacizumab, carboplatin and paclitaxel once every 3 weeks, for at least 6 cycles, until disease progression (as assessed by the investigator), unacceptable toxicity, physician or participant decision or withdrawal of consent. If either chemotherapy or bevacizumab is discontinued, the participant may continue to receive the other ongoing therapy.
干预措施: Bevacizumab (Drug)
Bevacizumab in Combination with Carboplatin and Paclitaxel
Administration of bevacizumab, carboplatin and paclitaxel once every 3 weeks, for at least 6 cycles, until disease progression (as assessed by the investigator), unacceptable toxicity, physician or participant decision or withdrawal of consent. If either chemotherapy or bevacizumab is discontinued, the participant may continue to receive the other ongoing therapy.
干预措施: Carboplatin (Drug)
Bevacizumab in Combination with Carboplatin and Paclitaxel
Administration of bevacizumab, carboplatin and paclitaxel once every 3 weeks, for at least 6 cycles, until disease progression (as assessed by the investigator), unacceptable toxicity, physician or participant decision or withdrawal of consent. If either chemotherapy or bevacizumab is discontinued, the participant may continue to receive the other ongoing therapy.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Percentage of Participants with GI Perforation/Fistula Events by Grade According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
时间窗: Baseline up to 24 months
Percentage of Participants with GI-Vaginal Fistula Events by Grade According to NCI-CTCAE Version 4.0
时间窗: Baseline up to 24 months
Percentage of Participants with GU Fistula Events by Grade According to NCI-CTCAE Version 4.0
时间窗: Baseline up to 24 months
次要结局
- Time to First GI-Vaginal Fistula(Baseline up to 24 months)
- Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Bevacizumab During the Treatment Period(Baseline up to 24 months)
- Time to First GI Perforation/Fistula(Baseline up to 24 months)
- Time to First GU Fistula(Baseline up to 24 months)
- Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Carboplatin During the Treatment Period(Baseline up to 24 months)
- Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Paclitaxel During the Treatment Period(Baseline up to 24 months)
- Duration of Treatment for Bevacizumab(Baseline up to 24 months)
- Duration of Treatment for Carboplatin(Baseline up to 24 months)
- Duration of Treatment for Paclitaxel(Baseline up to 24 months)
- Percentage of Participants with Adverse Events (AEs)(Baseline up to 24 months)
- Percentage of Participants with Serious Adverse Events (SAEs)(Baseline up to 24 months)
- Percentage of Participants with Adverse Events of Special Interest (AESIs)(Baseline up to 24 months)
- Percentage of Participants with AEs Leading to Treatment Interruption or Permanent discontinuation(Baseline up to 24 months)
- Percentage of Deaths Causally Related to Treatment(Baseline up to 24 months)
- Progression-Free Survival (PFS) According to Response Evaluation Criteria for Solid Tumors (RECIST) Version 1.1(Baseline up to 24 months)
- Overall Survival (OS)(Baseline up to 24 months)
- Percentage of Participants with a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1(Baseline up to 24 months)