A Phase 1 Trial of Lapatinib in Combination With 1) Sirolimus or 2) Metformin in Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Lapatinib in Combination with Sirolimus or Metformin
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of 2 different combinations of drugs that can be given to patients with advanced cancer. The first combination of drugs is Tykerb (lapatinib) and Rapamune (sirolimus), and the second combination is lapatinib and Glucophage (metformin). The safety of these drug combinations will also be studied.
详细描述
The Study Drugs:
Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking 2 proteins on the surface of the cancer cell, which are HER 1 and HER 2 receptors.
Sirolimus is designed to block a protein called mammalian target of rapamycin (mTOR) (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.
Metformin was designed to treat patients with diabetes. It may be able to block mTOR and slow the growth of tumors.
Study Drug Groups:
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
- •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 at least 3 weeks beyond their previous cytotoxic treatment. Patient must wait at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; In addition, patients must be at least 3 weeks beyond the last session of radiation therapy or major surgery. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status should be less or equal to 3
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count (ANC) >/= 750/mL; platelets >/= 50,000/mL; creatinine </= 2x upper limit of normal (ULN) for the Sirolimus Arm and creatinine < 1.5 mg/dl for the Metformin arm; total bilirubin </=2.0 (For patients with Gilbert syndrome, bilirubin level > 2 could will be allowed on study if the hyperbilirubinemia is believed to be secondary only to the Gilbert syndrome); ALT (SGPT) </= 5x ULN; Exception for patients with liver metastasis: total bilirubin </= 3x ULN; ALT (SGPT) </= 8x 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
- •Patients with treated brain metastases are allowed in both arms of the study.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- •Pregnant or lactating women.
- •History of hypersensitivity to Lapatinib or any component of the formulation.
- •Patients who have malabsorption syndrome
- •Patients with class III or IV congestive heart failure as defined by New York Heart Association functional classification system
- •Patients unwilling or unable to sign informed consent document
- •History of hypersensitivity to Sirolimus or any component of the formulation (for Lapatinib and Sirolimus arm only)
- •History of hypersensitivity to metformin or any component of the formulation (for Lapatinib and Metformin arm only)
研究组 & 干预措施
Lapatinib + Metformin
Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Metformin Starting oral dose 1000 mg daily.
干预措施: Lapatinib (Drug)
Lapatinib + Sirolimus
Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Sirolimus starting oral dose 1 mg daily.
干预措施: Lapatinib (Drug)
Lapatinib + Sirolimus
Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Sirolimus starting oral dose 1 mg daily.
干预措施: Sirolimus (Drug)
Lapatinib + Metformin
Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Metformin Starting oral dose 1000 mg daily.
干预措施: Metformin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Lapatinib in Combination with Sirolimus or Metformin
时间窗: 21 day cycle
MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is less than 33%.
次要结局
未报告次要终点