Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 278
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of bevacizumab (Avastin) and temsirolimus (Torisel) that can be given with 1 of 3 other study drugs --carboplatin (Paraplatin), paclitaxel (Taxol), or sorafenib (Nexavar). The safety of these drug combinations will also be studied.
详细描述
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
Temsirolimus is designed to block the growth of cancer cells, which may eventually cause the cancer cells to die.
Carboplatin is designed to damage the DNA (the genetic material of cells)of cancer cells, which may will eventually cause the cancer cells to die.
Paclitaxel is designed to damage the DNA of cancer cells, which may eventually cause the cancer cells to die.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Inclusion: (For all treatment arms)
- •1.1 Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- •1.2 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 does not target the only measurable or evaluable disease.
- •1.3 Patients must have measurable or evaluable disease
- •1.4 ECOG performance status </= 2 (Karnofsky >/= 60%, Lansky >/= 50%).
- •1.5 Patients must have normal organ function defined as: creatinine </= 1.5 x ULN for children and </= 2.0 x ULN for adults; total bilirubin </= 2.0; ALT(SGPT)/AST (SGOT) </= 5 X ULN. In patients with significant liver disease and chronically elevated liver transaminases, ALT/AST may be elevated as high as 8 X ULN.
- •1.6 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.
- •1.7 Ability to understand and the willingness to sign a written informed consent document.
- •1.8 Life expectancy of at least 3 months.
- •1.9 Patients may not be receiving any other experimental agents and/or any other concurrent anticancer agents or therapies except hormonal maintenance.
- •Inclusion: (For carboplatin and paclitaxel arms)
- •2.1 Patients must have normal marrow function defined as: absolute neutrophil count >/= 1,500/mL; platelets >/= 100,000/mL.
- •2.2 Patient with neuropathies of CTC grade 1 or less.
- •Inclusion: (For sorafenib arm)
- •3.1 Patients must have normal marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/= 75,000/mL.
排除标准
- •Exclusion: (For all treatment arms)
- •4.1 Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- •4.2 Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
- •4.3 Patients with clinically significant cardiovascular disease: History of CVA within 6 months Myocardial infarction or unstable angina within 6 months Unstable angina pectoris New York Heart Association Class > II
- •4.4 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day
- •4.5 Pregnant or lactating women.
- •4.6 History of hypersensitivity to bevacizumab or murine products, temsirolimus or its metabolites, or any component of the formulation.
- •4.7 Patients with hemorrhagic brain metastases.
- •4.8 Patients with prior abdominal surgery within 30 days prior to entering the study.
- •4.9 Medications with potent inducer or inhibitor of P450 3A4 should be avoided within 5 half lives of temsirolimus.
- •Exclusion: (For carboplatin treatment arm)
- •5.1 Hypersensitivity to carboplatin or any component of the formulation.
- •Exclusion: (For paclitaxel treatment arm)
- •6.1 Hypersensitivity to paclitaxel or any component of the formulation.
- •Exclusion: (For sorafenib treatment arm)
- •7.1 History of hypersensitivity to sorafenib or any component of the formulation.
研究组 & 干预措施
Sorafenib Group
Sorafenib: Starting dose 200 mg by mouth daily for a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Bevacizumab (Drug)
Sorafenib Group
Sorafenib: Starting dose 200 mg by mouth daily for a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Sorafenib (Drug)
Carboplatin Group
Carboplatin: Starting dose AUC 2 by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Bevacizumab (Drug)
Carboplatin Group
Carboplatin: Starting dose AUC 2 by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Carboplatin (Drug)
Carboplatin Group
Carboplatin: Starting dose AUC 2 by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Temsirolimus (Drug)
Paclitaxel Group
Paclitaxel: Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Bevacizumab (Drug)
Paclitaxel Group
Paclitaxel: Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Temsirolimus (Drug)
Paclitaxel Group
Paclitaxel: Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Paclitaxel (Drug)
Sorafenib Group
Sorafenib: Starting dose 200 mg by mouth daily for a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
干预措施: Temsirolimus (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 4 weeks
MTD defined by dose-limiting toxicities (DLTs) that occur during the first four weeks of therapy. DLT defined as any grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v4.0.
次要结局
- Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Carboplatin(56 days)
- Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Paclitaxel(56 days)
- Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Sorafenib(56 days)