A Phase I Trial of Doxil, Bevacizumab and Temsirolimus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Maximum tolerated doses (MTDs) and Dose-limiting toxicities (DLTs)
研究概览
简要总结
The goal of this clinical research study is to learn the highest safe doses of the combination of Doxil (liposomal doxorubicin), Avastin (bevacizumab), and Torisel (Temsirolimus) that can be given to patients with advanced cancer that has spread or is unable to be surgically removed. The safety and effectiveness of this combination of drugs will also be studied.
详细描述
The Study Drugs:
Liposomal doxorubicin is designed to cause cancer cells to be fragile, which may cause the cancer cells to die.
Bevacizumab is designed to block or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients for tumor growth.
Temsirolimus is designed to block the growth of cancer cells, which may eventually cause the cancer cells to die.
Everolimus is designed to block a protein called mammilian target of rapamycin (mTOR) inside the cancer cells, which is involved in cancer cell growth.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 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 has no standard therapy that improves survival by at least three months.
- •All patients must have an estimated life expectancy of at least 12 weeks.
- •Patients must have measurable or evaluable disease
- •Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available.
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have organ and marrow function defined as: absolute neutrophil count >/= 1,500/mL; platelets >/=100,000/mL; creatinine </= 3 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN. In patients with significant liver disease and chronically elevated liver transaminases, ALT may be elevated as high as 8 X ULN.
- •Cardiac ejection fraction >/= 50% without evidence of congestive heart failure (CHF).
- •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, for the duration of study participation, and for 90 days after the last dose.
- •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 hormonal maintenance treatment for prostate cancer.
排除标准
- •Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
- •Poorly controlled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)
- •Patients with clinically significant cardiovascular disease: - History of cerebral vascular accident (CVA) within 6 months - Myocardial infarction or unstable angina within 6 months - Unstable angina pectoris - New York Heart Association Class CHF score ≥ II
- •Prior cumulative doxorubicin dose > 300 mg/m2
- •Pregnant or lactating women
- •History of hypersensitivity to doxil, doxorubicin, HCL, temsirolimus or it's metabolites (including sirolimus), polysorbate 80, bevacizumab or murine products
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- •Patients < 12 years of age
- •Inability to swallow tablets for everolimus arm.
研究组 & 干预措施
Doxil, Bevacizumab + Temsirolimus
Doxil day 1 of each 21 day cycle, beginning dose level 10 mg/m^2 by vein over 3 hours.
Bevacizumab day 1 of each 21 day cycle, beginning dose level 5 mg/kg by vein over 90 minutes.
Temsirolimus days 1, 8 & 15 of 21 Day Cycle, beginning dose level 12.5 mg by vein over 30 to 60 minutes.
干预措施: Doxil (Drug)
Doxil, Bevacizumab + Temsirolimus
Doxil day 1 of each 21 day cycle, beginning dose level 10 mg/m^2 by vein over 3 hours.
Bevacizumab day 1 of each 21 day cycle, beginning dose level 5 mg/kg by vein over 90 minutes.
Temsirolimus days 1, 8 & 15 of 21 Day Cycle, beginning dose level 12.5 mg by vein over 30 to 60 minutes.
干预措施: Bevacizumab (Drug)
Doxil, Bevacizumab + Temsirolimus
Doxil day 1 of each 21 day cycle, beginning dose level 10 mg/m^2 by vein over 3 hours.
Bevacizumab day 1 of each 21 day cycle, beginning dose level 5 mg/kg by vein over 90 minutes.
Temsirolimus days 1, 8 & 15 of 21 Day Cycle, beginning dose level 12.5 mg by vein over 30 to 60 minutes.
干预措施: Temsirolimus (Drug)
结局指标
主要结局
Maximum tolerated doses (MTDs) and Dose-limiting toxicities (DLTs)
时间窗: First cycle (21 days)
MTD defined as dose level below dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) in first cycle. Dose limiting toxicity (DLT) defined as any grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to the study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by NCI-CTCAE), despite supportive care; any Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.
次要结局
- Anti-Tumor Efficacy of Drug Combination(4 months)