An Open Label, Randomized Phase I/IIa Trial Evaluating MK-0646 in Combination With Erlotinib (TARCEVA™) for Patients With Recurrent Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 95
- 主要终点
- Phase I: Number of Participants Experiencing at Least One Dose-Limiting Toxicity (DLT) Adverse Event (AE) During the First Four Weeks of Dalotuzumab Plus Erlotinib Treatment
研究概览
简要总结
This is a Phase I/IIa study to evaluate safety and efficacy of dalotuzumab (MK-0646) in combination with erlotinib in participants with recurrent Non-Small Cell Lung Cancer (NSCLC). The Phase I part of this study will determine the highest tolerated dose of dalotuzumab to be given in combination with erlotinib. The primary hypothesis for the Phase I part of the study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC is generally well-tolerated as evidenced by accumulated safety data from this trial. The Phase II part of this study will investigate how well dalotuzumab works in conjunction with erlotinib at treating recurrent NSCLC. The primary hypothesis for the Phase II part of this study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC results in improvement in Progression Free Survival (PFS) compared to participants treated with erlotinib alone. PFS is defined as the time from randomization until either the emergence of radiographic evidence of disease progression (as documented by an independent core laboratory) or death due to any cause, whichever occurs first.
详细描述
Dalotuzumab is a humanized monoclonal antibody (mAb) that targets the Insulin-like Growth Factor Receptor (IGF-1R). Dalotuzumab may act through:
- Inhibition of IGF-1-mediated cell signaling to cause reductions in tumor growth and spread
- Antibody dependent cell-mediated cytotoxicity
In preclinical studies, dalotuzumab improved the activity of an anti-Epidermal Growth Factor Receptor (EGFR) mAb and the activity of Erlotinib, a small molecule inhibitor of EGFR
Trial Duration of Treatment: Participants will continue on the study for as long as their disease is not progressing and they do not have unmanageable side effects from the treatment.
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
- •Participant has locally advanced or metastatic stage IIIB/IV NSCLC that has relapsed after hemotherapy/chemoratiotherapy
- •Participant has had at least one chemotherapy regimen for recurrent or metastatic disease
- •Participant is 18 years of age or older
- •Participant has a performance status of 0-2 on Eastern Cooperative Group (ECOG) scale
- •Women of childbearing potential have a negative pregnancy test
排除标准
- •Participant has had chemotherapy within 2 weeks or biological therapy (e.g. bevacizumab) within 4 weeks
- •Participant has not recovered from adverse events from previous therapy within 4 weeks
- •Participant has received EGFR-Tyrosine Kinase Inhibitor (TKI) inhibitor/anti-EGFR mAb therapy
- •Participant has received IGF1R-TKI inhibitor/anti-IGF1R mAB therapy
- •Participant has had more than 2 systemic chemotherapies for metastatic disease
- •Participant has not completed radiotherapy with complete resolution of toxicities at least 2 weeks before starting in the study
- •Participant is taking part in another clinical study
- •Participant has a primary central nervous system tumor
- •Participant abuses drugs or alcohol
- •Participant is pregnant or breastfeeding
- •Participant is Human Immunodeficiency Virus (HIV) positive
- •Participant has a history of hepatitis B or C
- •Participant is using growth hormone or growth hormone inhibitors
研究组 & 干预措施
Ph I: Dalotuzumab 5 mg/kg + Erlotinib
During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.
干预措施: Dalotuzumab (Drug)
Ph I: Dalotuzumab 10 mg/kg + Erlotinib
During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.
干预措施: Dalotuzumab (Drug)
Ph II: Dalotuzumab 10 mg/kg + Erlotinib
During the Phase II part of the study, participants are randomized to receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
干预措施: Dalotuzumab (Drug)
Ph II: Erlotinib
During the Phase II part of the study, participants are randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Phase I: Number of Participants Experiencing at Least One Dose-Limiting Toxicity (DLT) Adverse Event (AE) During the First Four Weeks of Dalotuzumab Plus Erlotinib Treatment
时间窗: Up to 4 weeks after initiation of treatment
A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy. Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever \>38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10\^9/L). Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab. Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.
Phase II: Median Progression Free Survival (PFS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment
时间窗: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)
PFS was defined as the time from randomization until either the emergence of radiographic evidence of disease progression or death due to any cause, whichever occurs first. Disease progression was classified as a radiographic assessment of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) using computed tomography (CT) or magnetic resonance imaging (MRI). As pre-specified by the protocol, final analysis of PFS was to take place after approximately 49 PFS events or deaths had occurred in the Phase II part of the trial. A non-parametric Kaplan-Meier method was used to estimate the median PFS time for each treatment group. Participants who discontinued from the study for reasons other than progression of disease were treated as right-censored observations at the time of the last response evaluation. Participants who withdrew from the study due to PD were considered to have a disease progression between the last visit and the time of withdrawal.
次要结局
- Phase II: Median Overall Survival (OS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment(Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date))
- Phase II: Percentage of Participants With Complete Response (CR) or Partial Response (PR) After Dalotuzumab Plus Erlotinib Treatment (Objective Response Rate [ORR])(Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date))