A Phase-I Study Of Cyclical Oral Administration Of Temozolomide In Combination With PEG12000-Interferon Alfa-2B In Patients With Refractory And/Or Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PEG-interferon alfa-2B may interfere with the growth of cancer cells. Combining temozolomide with PEG-interferon alfa-2B may be an effective treatment for advanced solid tumors.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and PEG-interferon alfa-2B in treating patients who have advanced solid tumors.
详细描述
OBJECTIVES:
- Determine the safety and tolerability of temozolomide and PEG-interferon alfa-2b in patients with advanced refractory solid tumors or chemotherapy-naive advanced cancer.
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of this regimen in this patient population.
- Determine the pharmacokinetics of PEG-interferon alfa-2b at the MTD when administered with temozolomide in this patient population.
- Determine the anti-tumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral temozolomide on days 1-7 and 15-21 and PEG-interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-9 patients receive escalating doses of temozolomide and PEG-interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced solid tumor that is refractory to standard therapy OR
- •Histologically confirmed chemotherapy-naive advanced cancer for which no curative therapy or higher priority palliative chemotherapy exists
- •Brain metastasis allowed
- •No bone marrow involvement of tumor
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Absolute neutrophil count greater than 1,500/mm^3 AND/OR
- •Platelet count greater than 100,000/mm^3
- •ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
- •No autoimmune hepatitis
- •Creatinine less than 2.5 times ULN
- •Cardiovascular:
- •No severe coronary artery disease
- •No congestive heart failure
- •No severe chronic obstructive pulmonary disease
- •Gastrointestinal:
- •No frequent vomiting
- •No medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction, partial intestinal bypass, or external biliary diversion)
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •No known or suspected hypersensitivity to imidazotetrazin, interferon alfa, or any excipient or vehicle included in the formulation or delivery system of study drug
- •No history of autoimmune disease
- •No preexisting severe psychiatric condition or history of severe psychiatric disorder (including suicidal ideation or attempt)
- •No life-threatening condition or severe preexisting condition
- •No uncontrolled thyroid abnormalities
- •No nonmalignant systemic disease
- •No active uncontrolled infection
- •HIV negative
- •No AIDS-related illness
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 3 weeks since prior biologic agents (e.g., bi-specific antibodies, interleukin-2, or interferon) and recovered (excluding alopecia)
- •No prior allogeneic, syngeneic, or autologous bone marrow or stem cell transplantation
- •No other concurrent biologic therapy
- •No concurrent colony stimulating factors or epoetin alfa for the prevention of myelotoxicity
- •Chemotherapy:
- •See Disease Characteristics
- •At least 4 weeks since prior chemotherapy (more than 6 weeks for nitrosoureas, melphalan, or mitomycin) and recovered (excluding alopecia)
- •No prior high-dose chemotherapy and stem cell transplantation
- •No more than 3 prior chemotherapy regimens
- •No other concurrent chemotherapy
- •Endocrine therapy:
- •Not specified
- 另有 8 项未显示
排除标准
- 未提供
研究者
Lionel.D.Lewis, MD
Professor of Medicine and of Pharmacology and Toxicology
Dartmouth-Hitchcock Medical Center