A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination With Irinotecan Versus Cetuximab and Irinotecan for Patients With Metastatic Rectal Cancers (mRC) Expressing High IGF-1/Low IGF-2 Levels
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 主要终点
- Assessment of Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab + irinotecan. The primary hypothesis is that administration of dalotuzumab in combination with irinotecan to participants with wild-type KRAS metastatic rectal carcinoma with high insulin growth factor (IGF)-1/low IGF-2 expression levels improves progression-free survival compared to patients treated with cetuximab in combination with irinotecan.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Has metastatic colorectal cancer with primary tumor originating from the rectum
- •Has an available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies
- •Has at least one measurable lesion greater than or equal to 10 mm
- •Disease has progressed after treatment with both irinotecan- and oxaliplatin-containing regimens and should have progressed on or within 3 months of completing their last line of therapy
- •Has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
排除标准
- •Has poorly-controlled diabetes
- •Has received chemotherapy or biological therapy within 2 weeks prior to initial dosing on this study, or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior surgery
- •Has received radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain
- •Is currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study
- •Was unable to complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure)
- •Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors
- •Has a known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has primary CNS tumor
- •Has a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma; potentially curative therapy with no evidence of that disease for 5 years, deemed low risk for recurrence by treating physician.
- •Is human immunodeficiency virus (HIV)-positive
- •Has active hepatitis B or C infection and is receiving antiviral treatment regimens
- •Has symptomatic ascites or pleural effusion
- •Is concurrently using growth hormone (GH), or growth hormone inhibitors
研究组 & 干预措施
Arm A: Dalotuzumab + Irinotecan
Participants receive irinotecan intravenously (IV), 180 mg/m^2 once every two weeks + dalotuzumab IV, 10 mg/kg once weekly, during ≥1 42-day treatment cycle(s).
干预措施: Dalotuzumab (Drug)
Arm A: Dalotuzumab + Irinotecan
Participants receive irinotecan intravenously (IV), 180 mg/m^2 once every two weeks + dalotuzumab IV, 10 mg/kg once weekly, during ≥1 42-day treatment cycle(s).
干预措施: Irinotecan (Drug)
Arm B: Cetuximab + Irinotecan
Participants receive cetuximab IV, initial dose of 400 mg/m^2 and then 250 mg/m^2 IV weekly + irinotecan IV, 180 mg/m^2 once every two weeks, during ≥1 42-day treatment cycle(s).
干预措施: Irinotecan (Drug)
Arm B: Cetuximab + Irinotecan
Participants receive cetuximab IV, initial dose of 400 mg/m^2 and then 250 mg/m^2 IV weekly + irinotecan IV, 180 mg/m^2 once every two weeks, during ≥1 42-day treatment cycle(s).
干预措施: Cetuximab (Drug)
结局指标
主要结局
Assessment of Progression-free Survival (PFS)
时间窗: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
PFS is a measure of the time from randomization to the time of first documented disease progression (assessed by an independent Radiology Review Committee \[iRRC\]) or participant death, whichever occurs first.
次要结局
- Percentage of Participants With Objective Response Rate (ORR)(From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years))