A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Consolidation Progression-Free Survival
研究概览
简要总结
The purpose of this research study is to evaluate how patients with newly diagnosed advanced ovarian, fallopian tube, primary peritoneal cancer and papillary serous or clear cell mullerian tumors respond to consolidation therapy with Avastin and erlotinib or Avastin alone over 1 year. These drugs have been used in the treatment of other types of cancers and information from those studies suggests that these agents may help to treat the cancers studied here.
详细描述
Objectives:
Primary To examine the progression free survival (PFS) of Avastin and Erlotinib (AE) or Avastin (A) as consolidation therapy.
Secondary To examine the toxicity between the two consolidative regimens AE vs. A. To assess the response rate of CTA.
STATISTICAL DESIGN This study uses a randomized selection design. Both consolidation treatment arms are deemed experimental and are compared against a historical control [McGuire WP et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. NEJM 1996: 334:1-6. PMID:7494563]. With 30 patients in a given arm and 6 months of follow-up, there was 80% power to detect a 61.5% increase in median PFS from 13 months to 21 months assuming 1-sided 10% significance.
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
- 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
- •18 years of age and older
- •Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, primary peritoneal carcinoma, or papillary serous mullerian carcinoma
- •Previous attempted surgical debulking
- •Stage III or IV
- •Willing and able to undergo second look laparoscopy
- •Performance status 0-1 by ECOG scale
- •Peripheral neuropathy < grade 2
- •Life expectancy of 6 months or greater
排除标准
- •Patients with clinically significant cardiovascular disease as outlined in the protocol
- •Neutrophil count < 1,500/mm3; platelet count <100,000/m3
- •Alkaline phosphatase or bilirubin > 1.5 x ULN, SGOT > 5 x ULN
- •Calculated creatinine clearance < 50ml/min
- •Prior chemotherapy or radiotherapy for other malignancy except for the treatment for localized breast cancer greater than five years prior to diagnosis
- •No more than one cycle of first line chemotherapy with carboplatin and paclitaxel
- •Inadequate surgical cytoreduction such that interval cytoreductive surgery could materially improve prognosis
- •Concurrent invasive malignancy
- •Evidence of bleeding diathesis or coagulopathy
- •Evidence of tumor involving major blood vessels on any prior CT scans
- •Surgical wound that has failed to close
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of this study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0
- •Serious non-healing wound, ulcer, or bone fracture
- •Prior treatment with an anti-angiogenic agent
- •Any active bleeding
- •Active psychiatric disease or neurologic symptoms requiring treatment
- •Presence of central nervous system brain metastases
- •Proteinuria at screening as demonstrated by criteria in protocol
- •Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent
- •Known hypersensitivity to Cremophor EL or any component of Avastin
- •Active bacterial, viral, or fungal infections
- •Receiving any other investigational agent
- •History of gastrointestinal perforation
- •Prior therapies targeting the epidermal growth factor receptor
- •Symptoms of bowel obstruction
- •Dependence on TPN or IV hydration
研究组 & 干预措施
carboplatin/paclitaxel/bevacizumab then bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.
干预措施: bevacizumab (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.
干预措施: paclitaxel (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.
干预措施: carboplatin (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
干预措施: bevacizumab (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
干预措施: erlotinib (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
干预措施: paclitaxel (Drug)
carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
干预措施: carboplatin (Drug)
carboplatin/paclitaxel/bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation: None
干预措施: bevacizumab (Drug)
carboplatin/paclitaxel/bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation: None
干预措施: paclitaxel (Drug)
carboplatin/paclitaxel/bevacizumab
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2.
Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.
Consolidation: None
干预措施: carboplatin (Drug)
结局指标
主要结局
Consolidation Progression-Free Survival
时间窗: Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.
Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to \>/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.
Consolidation Treatment-related Toxicity Rate
时间窗: Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.
Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.
次要结局
- Consolidation Objective Response Rate(Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.)
研究者
Susana M. Campos, MD
Medical Oncologist.
Dana-Farber Cancer Institute