A Phase I Trial of Dasatinib (Src Inhibitor), Bevacizumab (Anti-VEGF Monoclonal Antibody) and Metronomic Paclitaxel + or - Methylnaltrexone in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Dasatinib, Bevacizumab and Paclitaxel + or - Methylnaltrexone in Advanced or Metastatic Cancer That is Refractory to Standard Treatment
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 dasatinib, bevacizumab, and paclitaxel with or without Methylnaltrexone that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.
Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells.
Paclitaxel is designed to block cancer cells from dividing, which may cause them to die.
Methylnaltrexone is designed to block the constipating effect of opioid analgesics on the gastrointestinal tract. It is also capable of blocking the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells.
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
- 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 who have no standard therapy available that improves survival by at least three months.
- •Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. After targeted/biologic therapy a patient has to be off treatment for 5 half-lives or 3 weeks whatever is shorter.
- •ECOG performance status </=
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=90,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN.
- •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 30 days after the last dose.
- •Patients must be able to understand and be willing to sign a written informed consent document.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- •Patients with hemoptysis within 28 days prior to entering the study.
- •Patients with clinically significant unexplained bleeding within 28 days prior to the first dose of study medication.
- •Uncontrolled systemic vascular hypertension (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg on medication).
- •Patients with clinically significant cardiovascular disease: history of CVA within 6 months; myocardial infarction or unstable angina within 6 months.
- •Major surgery within 28 days prior to Day 1 of dosing Bevacizumab.
- •Pregnant or lactating women.
- •History of hypersensitivity to dasatinib or any component of the formulation.
- •History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- •History of hypersensitivity to paclitaxel or any component of the formulation.
- •Patients with pleural effusion which is considered clinically significant by the attending physician.
- •Patients unwilling or unable to sign informed consent document.
- •Social situations that would limit compliance with study requirements.
- •Patients receiving opioids within 2 weeks before signing the consent and patients, who cannot be off opioids until initiating the study medication (for methylnaltrexone arm only).
研究组 & 干预措施
Dasatinib, Bevacizumab + Paclitaxel
Dose Escalation Starting Dose Levels: 50 mg Dasatinib daily by mouth (PO), 5 mg/kg Bevacizumab IV on Day 1 and 15; Paclitaxel 40 mg/m2 IV on Day 1, 8 and 15
Dose Expansion Starting Dose Levels: Maximum tolerated dose from Dose Escalation.
干预措施: Dasatinib (Drug)
Dasatinib, Bevacizumab + Paclitaxel
Dose Escalation Starting Dose Levels: 50 mg Dasatinib daily by mouth (PO), 5 mg/kg Bevacizumab IV on Day 1 and 15; Paclitaxel 40 mg/m2 IV on Day 1, 8 and 15
Dose Expansion Starting Dose Levels: Maximum tolerated dose from Dose Escalation.
干预措施: Bevacizumab (Drug)
Dasatinib, Bevacizumab + Paclitaxel
Dose Escalation Starting Dose Levels: 50 mg Dasatinib daily by mouth (PO), 5 mg/kg Bevacizumab IV on Day 1 and 15; Paclitaxel 40 mg/m2 IV on Day 1, 8 and 15
Dose Expansion Starting Dose Levels: Maximum tolerated dose from Dose Escalation.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Dasatinib, Bevacizumab and Paclitaxel + or - Methylnaltrexone in Advanced or Metastatic Cancer That is Refractory to Standard Treatment
时间窗: Continuous assessment during each dose level/28-day cycle
MTD defined as the highest dose below any dose that has one third or more patients with dose limiting toxicities (DLT).
次要结局
- Antitumor Efficacy of the Combination of Dasatinib, Bevacizumab and Paclitaxel + or - Methylnaltrexone in Advanced or Metastatic Cancer That is Refractory to Standard Treatment(28 days after the last dose of study drugs)