A Phase I and Randomized Phase II Trial of Gemcitabine + Erlotinib (NSC-718781) + IMC-A12 (NSC-742460) vs. Gemcitabine + Erlotinib as First-Line Treatment in Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 146
- 主要终点
- Maximum Tolerated Dose Determination
研究概览
简要总结
This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies 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. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I) II. To assess progression-free survival in patients with metastatic pancreatic cancer treated with IMC-A12 plus gemcitabine and erlotinib compared to those treated with gemcitabine plus erlotinib alone. (Phase II) III. To assess overall survival in each of the two treatment arms in this group of patients. (Phase II) IV. To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in each of the two treatment arms in the subset of this group of patients with measurable disease. (Phase II) V. To assess the qualitative and quantitative toxicities in each of the two treatment arms in this group of patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of cixutumumab followed by a randomized, phase II study.
Patients are initially enrolled into the phase I portion of the study to determine the recommended phase II dose (RPTD) of cixutumumab. Once the RPTD is determined, patients are enrolled into the phase II portion of the study.
PHASE I (LIMITED INSTITUTIONS): Patients receive erlotinib hydrochloride orally (PO) once daily on days 1-28, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
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 pancreatic adenocarcinoma
- •Stage IV disease (any T, any N, M1 [distant metastases])
- •Unresectable disease
- •Histologic diagnosis based on a metastatic site must be compatible with pancreatic cancer
- •Measurable and/or nonmeasurable disease
- •No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer
- •No macroscopic residual disease post-resection as the only site of disease
- •No clinically significant ascites
- •No known brain metastases
- •Patients with neurologic signs or symptoms must undergo brain imaging studies AND studies must be negative for disease
- •Zubrod performance status 0-1
- •ANC ≥ 1,500/mcL
- •Platelet count ≥ 100,000/mcL
- •Hemoglobin ≥ 9 g/dL
- •Leukocytes ≥ 3,000/mcL
- •Total bilirubin normal
- •SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)
- •Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- •Fasting serum glucose < 120 mg/dL or below the ULN
- •Patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition
- •INR ≤ 1.5 and PTT ≤ 5 seconds above ULN
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Willing to submit previously collected tumor tissue specimens
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
- •No active acute or chronic infections requiring antibiotics
- •No significant ongoing cardiac problems, including any of the following:
- •Myocardial infarction within the past 6 months
- •Uncontrolled hypertension
- •Unstable angina
- •Uncontrolled arrhythmia
- •Congestive heart failure
- •No known HIV infection
- •No other prior malignancy, except for the following:
- •Adequately treated basal cell or squamous cell skin cancer
- •Carcinoma in situ of the cervix
- •Adequately treated stage I or II cancer from which the patient is currently in complete remission
- •Any other cancer from which the patient has been disease-free for 5 years
- •At least 14 days since prior surgery
- •At least 28 days since prior radiotherapy for palliation to metastatic sites
- •Patient must have other untreated metastatic sites that would qualify them for this protocol
- •At least 6 months since prior adjuvant chemotherapy
- •No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for advanced or locally advanced pancreatic cancer, including drugs that target either EGFR or IGFR
- •No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer
- •No prior gemcitabine hydrochloride
- •No prior chimerized or murine monoclonal antibody therapy
- •No concurrent CYP3A4 inducers including, but not limited to, any of the following:
- •Rifampicin
- •Rifabutin
- •Rifapentine
- 另有 19 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (erlotinib, gemcitabine, cixutumumab)
Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: cixutumumab (Biological)
Arm I (erlotinib, gemcitabine, cixutumumab)
Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Arm I (erlotinib, gemcitabine, cixutumumab)
Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: gemcitabine hydrochloride (Drug)
Arm II (erlotinib, gemcitabine)
Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Arm II (erlotinib, gemcitabine)
Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: gemcitabine hydrochloride (Drug)
结局指标
主要结局
Maximum Tolerated Dose Determination
时间窗: 28 days
Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
Progression-Free Survival
时间窗: Up to 3 years
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
次要结局
- Overall Survival(Up to 3 years)
- Response(Up to 3 years)
- Toxicity(Up to 3 years)