An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 54
- 主要终点
- Objective Response (OR)
研究概览
简要总结
This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning.
The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate observed for the standard therapy only.
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
- •Male or female subjects aged ≥ 18 years
- •Histological or cytological documentation of adenocarcinoma of the colon or rectum
- •Suitable to receive mFOLFOX6 regimen as first line metastatic treatment
- •At least 1 measurable lesion as per RECIST version 1.1
- •Unresectable or unlikely becoming resectable metastatic disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy of at least 3 months
- •Adequate bone marrow, liver, and renal function
排除标准
- •Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented.
- •Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs)
- •Uncontrolled hypertension
- •Subjects with symptoms, signs, or history of brain metastases
- •Any hemorrhage or bleeding event ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks of start of study treatment
- •Sensory neuropathy (> CTCAE Grade 1), unresolved toxicity > CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia
研究组 & 干预措施
Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)
On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.
干预措施: Regorafenib (Stivarga, BAY73-4506) (Drug)
Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)
On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.
干预措施: Oxaliplatin (Drug)
Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)
On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.
干预措施: Folinic acid (Drug)
Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)
On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.
干预措施: 5-FU (mFOLFOX6) (Drug)
结局指标
主要结局
Objective Response (OR)
时间窗: From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.
OR was defined as the best tumor response (confirmed complete response \[CR\] or partial response \[PR\]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to \< 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.
次要结局
- Duration of Stable Disease (DOSD)(From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks)
- Disease Control (DC)(From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks)
- Progression-free Survival (PFS)(From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks)
- Duration of Response (DOR)(From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks)
- Overall Survival (OS)(From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks)