A Phase I Study of Temsirolimus, Topotecan, and Bortezomib in Patients With Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of combination treatment with temsirolimus, topotecan, and bortezomib
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of Torisel (temsirolimus), Hycamtin (topotecan hydrochloride), and Velcade (bortezomib) that can be given, in combination, to patients with advanced cancer that has spread or is unable to be surgically removed. The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Temsirolimus is designed to block pathways that control important events such as the growth of blood vessels that are vital for the growth of cancer. This may cause cancer cells to die.
Topotecan hydrochloride is designed to block the function of important proteins in cancer cells. These proteins, when active, allow a cell's genes to duplicate and for the cancer cells to divide.
Bortezomib is designed to block the function of important proteins in cancer cells. These proteins control the destruction of proteins in tumor cells, which is important for their growth. This may cause cancer cells to die.
Study Drug Dose Level:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months
- •Patients should be at least four weeks or 5 half lives from the last day of chemotherapy, and antibody or other biological therapy, whichever is shorter.
- •Patients should be at least four weeks from the last day of therapeutic radiation.
- •The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 or Karnofsky >/= 60%.
- •Patients must have allowable organ and marrow function defined as: Absolute neutrophil count >/= 1,000/mL, Platelets >/=75,000/mL, Serum creatinine </= 2 * Upper Limit of Normal (ULN), Total bilirubin </= 2 * ULN, aminotransferase (ALT or SGPT) </= 3 * ULN, Fasting total cholesterol <= 350 mg/dL and triglyceride level <= 400 mg/dL.
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and will be advised to avoid pregnancy for 3 months after completion of therapy.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies except for continuing on hormonal therapy in cases of prostate cancer.
- •Treatment on this study may begin within 24 hours after Phase 0 dose of temsirolimus.
排除标准
- •Patients with hemoptysis within 28 days prior to entering the study.
- •Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- •Patients with clinically significant cardiovascular disease: • History of CVA within 6 months • Myocardial infarction or unstable angina within 6 months • Unstable angina pectoris
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day
- •Pregnant or lactating women.
- •History of hypersensitivity to bortezomib or any component of the bortezomib formulation.
- •History of hypersensitivity to topotecan or any component of the topotecan formulation.
- •History of hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation.
研究组 & 干预措施
Torisel + Hycamtin + Velcade
Torisel starting Dose 5 mg Intravenously over 30-60 minutes, Days 1, 8, and 15 of 21 Day Cycle.
Hycamtin starting Dose 0.8 mg/m^2 Intravenously over 30-60 minutes on Days 1 and 8 of 21 Day Cycle.
Velcade starting Dose 0.3 mg/m^2 Intravenously over 1 minute on Days 1, 4, 8, and 11 of 21 Day Cycle.
干预措施: Torisel (Temsirolimus) (Drug)
Torisel + Hycamtin + Velcade
Torisel starting Dose 5 mg Intravenously over 30-60 minutes, Days 1, 8, and 15 of 21 Day Cycle.
Hycamtin starting Dose 0.8 mg/m^2 Intravenously over 30-60 minutes on Days 1 and 8 of 21 Day Cycle.
Velcade starting Dose 0.3 mg/m^2 Intravenously over 1 minute on Days 1, 4, 8, and 11 of 21 Day Cycle.
干预措施: Hycamtin (Topotecan) (Drug)
Torisel + Hycamtin + Velcade
Torisel starting Dose 5 mg Intravenously over 30-60 minutes, Days 1, 8, and 15 of 21 Day Cycle.
Hycamtin starting Dose 0.8 mg/m^2 Intravenously over 30-60 minutes on Days 1 and 8 of 21 Day Cycle.
Velcade starting Dose 0.3 mg/m^2 Intravenously over 1 minute on Days 1, 4, 8, and 11 of 21 Day Cycle.
干预措施: Velcade (Bortezomib) (Drug)
Expansion Group
Torisel + Hycamtin + Velcade Expansion Group
Addition of 10 participants at highest tolerated dose level
干预措施: Torisel (Temsirolimus) (Drug)
Expansion Group
Torisel + Hycamtin + Velcade Expansion Group
Addition of 10 participants at highest tolerated dose level
干预措施: Hycamtin (Topotecan) (Drug)
Expansion Group
Torisel + Hycamtin + Velcade Expansion Group
Addition of 10 participants at highest tolerated dose level
干预措施: Velcade (Bortezomib) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of combination treatment with temsirolimus, topotecan, and bortezomib
时间窗: 21 days
MTD is defined as the highest dose in which the incidence of a dose limiting toxicity (DLT) is \< 33%.
次要结局
未报告次要终点