A Phase I/Randomized Phase II Study of the Anti-IGF-1R Monoclonal Antibody IMC-A12 in Combination With Erlotinib Compared With Erlotinib Alone in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Safety and Tolerability of IMC-A12 in Combination With Erlotinib Hydrochloride as Graded by Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0 (DLTs During Cycle One)
研究概览
简要总结
This randomized phase I/II trial is studying the side effects and best dose of cixutumumab and to see how well erlotinib hydrochloride works when given together with or without cixutumumab in treating patients with stage III or stage IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether erlotinib hydrochloride is more effective when given together with or without cixutumumab in treating non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine a tolerable dose of IMC-A12 (cixutumumab) in combination with erlotinib (erlotinib hydrochloride) in the target NSCLC population to be administered in the randomized phase II study section.
II. To determine the difference in PFS between the anti-IGF-1R monoclonal antibody IMC-A12 in combination with erlotinib compared to erlotinib alone in the target NSCLC population.
SECONDARY OBJECTIVES:
I. To evaluate the safety, tolerability, and adverse event profile of IMC-A12 in combination with erlotinib in patients with advanced non-small cell lung cancer.
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
- •Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
- •Stage IIIA, IIIB, or IV disease
- •Mixed histology permitted provided small-cell elements are not present
- •Measurable disease, defined as ≥ 1unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •Must have failed ≥ 1 platinum-containing chemotherapy regimen
- •CNS metastases are eligible if received prior radiotherapy to site(s) of CNS metastatic disease, or have had definitive resection of CNS metastatic disease and have no overt evidence of neurological deficits, are not requiring anti-epileptics, remain asymptomatic, and have been off steroids for ≥ 8 weeks
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy > 3 months
- •Leukocytes ≥ 3,000/mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Hemoglobin ≥ 9 g/dL
- •Platelets ≥ 100,000/mm³
- •Total bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- •Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- •Fasting serum glucose < 120 mg/dL OR normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-IGF-1R recombinant monoclonal antibody IMC-A122 or erlotinib hydrochloride
- •No poorly controlled diabetes mellitus
- •Patients with a history of diabetes mellitus are eligible, provided their blood glucose is within normal range at screening and they are on a stable dietary or therapeutic regimen for this condition
- •No uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •No inability to take oral medications or, in the investigator's opinion, gastrointestinal conditions or abnormalities likely to influence the absorption of oral medications
- •No prior or concurrent exposure to other EGFR or IGFR inhibitors
- •Recovered from all prior therapy with acute effects resolved to ≤ grade 1
- •At least 28 days since prior anticancer or investigational agent (within predicted 5 half-lives of agent)
- •More than 4 weeks since prior radiotherapy to target lesions and documented disease progression at these sites
- •More than 2 weeks since prior radiotherapy to non-target lesions
- •More than 4 months since prior major surgery or hormonal therapy (other than replacement)
排除标准
- 未提供
研究组 & 干预措施
Arm I (Enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO once daily on days 1-21. Patients with documented disease progression may cross over and receive treatment on arm II.
干预措施: erlotinib hydrochloride (Drug)
Arm I (Enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO once daily on days 1-21. Patients with documented disease progression may cross over and receive treatment on arm II.
干预措施: laboratory biomarker analysis (Other)
Arm II (Enzyme inhibitor and monoclonal antibody therapy)
Patients receive erlotinib hydrochloride PO as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15.
干预措施: cixutumumab (Biological)
Arm II (Enzyme inhibitor and monoclonal antibody therapy)
Patients receive erlotinib hydrochloride PO as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15.
干预措施: erlotinib hydrochloride (Drug)
Arm II (Enzyme inhibitor and monoclonal antibody therapy)
Patients receive erlotinib hydrochloride PO as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Safety and Tolerability of IMC-A12 in Combination With Erlotinib Hydrochloride as Graded by Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0 (DLTs During Cycle One)
时间窗: From time of first dose up to 28 days
Patients were evaluable for cohort dose escalation/de-escalation decision making either if they experienced DLTs in cycle 1 or if they had completed 24 of the planned 28 days (85%) dosing of erlotinib and three of the four planned days of weekly dosing of cixutumumab (75%) in cycle 1 in cohorts 1 and 2 in the absence of DLTs. In cohort 3, patients were evaluable for tolerability if they had completed 18 days (85%) dosing of erlotinib and had received the planned day 1 dose of cixutumumab.
次要结局
未报告次要终点