A Multi-center, Open-label Clinical Trial to Evaluate the Objective Response Rate of Bevacizumab in Combination With Modified FOLFOX-6 Followed by One Year of Maintenance With Bevacizumab Alone in Patients With Initially Not or Borderline Resectable Colorectal Liver Metastases (The CLMO-001 Trial)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 11
- 主要终点
- Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)
研究概览
简要总结
The multicenter, open-label, single-arm, non-randomized, two-stage Simon's design, phase II study (The CLMO-001 Trial) will evaluate the efficacy and safety of bevacizumab in combination with mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil [5-FU] and oxaliplatin) in participants with colorectal cancer and liver metastases. Participants will receive combination therapy of bevacizumab 5 milligrams per kilogram (mg/kg) intravenous (IV) dose and mFOLFOX-6 every 2 weeks during Cycles 1-5 and Cycles 7-12. Participants will receive mFOLFOX-6 alone (without bevacizumab) on Cycle 6. In between Cycle 6 and 7, participants will undergo liver surgery if operable. Thereafter participants will receive bevacizumab (5 mg/kg IV every 2 weeks) alone for 52 weeks (26 cycles) after the end of the post-operative phase (maintenance therapy). At the end of the preoperative treatment phase (Cycles 1-6), participants showing different alternative conditions admitted by the protocol will undergo different management (alternative study designs 1 to 3).
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
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants (male or female), greater than (>) 18 years of age
- •Histologically confirmed adenocarcinoma of the colon or the rectum
- •Primitive lesion is at a distance >12 centimeter (cm) from the anal margin for participants with primitive rectal tumor
- •Measurable metastatic disease confined to the liver
- •Eastern cooperative oncology group (ECOG) performance status 0-1
- •No previous chemotherapy for metastatic disease or treatment with drugs targeting vascular endothelial growth factor receptor (VEGF) or epidermal growth factor receptor (EGFR)
- •Adequate bone marrow, liver and renal function
- •Urine analysis with proteinuria less than (<) 2+
- •Use of at least one approved contraceptive method by participants with reproductive potential
- •Written informed consent from the participants
- •Surgical criteria for hepatic resection
- •Adjuvant treatment (either only surgery on primitive tumor or surgery on primitive tumor + adjuvant chemotherapy) must have been concluded greater than or equal to (>/=) 6 months before enrollment
排除标准
- •Presence of extrahepatic metastases
- •Evidence of lumbo-aortic and celiac lymph nodes involvement
- •Radiotherapy within 4 weeks before study start
- •History of inflammatory bowel disease and/or acute/sub-acute bowel occlusion
- •Presence of serious non-healing wound or ulcer
- •Evidence of bleeding diathesis or coagulopathy
- •Clinically significant cardiovascular disease
- •Uncontrolled hypertension
- •Current or recent ongoing treatment with anticoagulants
- •Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
- •Treatment with any investigational drug within 30 days prior to enrollment
- •Known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications
- •Co-existing malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. Interval between endoscopic biopsy or colorectal stenting and bevacizumab administration should be evaluated by oncologist/endoscopist
- •Pregnant or lactating women
- •Any other disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complication
- •Participants with known Human immunodeficiency virus (HIV) infection
- •Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection with concomitant cirrhosis or undergoing active treatment for the same
- •Participants who are unable or unwilling to comply with the requirements of the protocol and follow-up procedures
研究组 & 干预措施
Bevacizumab + mFOLFOX-6
Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).
干预措施: 5-Fluorouracil (5-FU) (Drug)
Bevacizumab + mFOLFOX-6
Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).
干预措施: Bevacizumab (Drug)
Bevacizumab + mFOLFOX-6
Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).
干预措施: Levofolinic acid (Drug)
Bevacizumab + mFOLFOX-6
Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)
时间窗: Up to 11 cycles of treatment (up to Week 22)
ORR was defined as the percentage of participants with shrinkage (PR) or disappearance of cancer (CR). Tumor response was evaluated according to the RECIST v1.1. The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of CT scan (abdomen + pelvis + chest) or CE-MRI (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set
时间窗: Up to 11 cycles of treatment (up to Week 22)
ORR was defined as the percentage of participants with shrinkage (partial response \[PR\]) or disappearance of cancer (complete response \[CR\]). Tumor response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
- Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection(End of study up to approximately 3 years)
- Overall Survival (OS)(End of study up to approximately 3 years)
- Progression-Free Survival (PFS)(End of study up to approximately 3 years)
- Disease-free Interval (DFI)(End of study up to approximately 3 years)