Phase I Study of Pazopanib in Combination With Lapatinib or Trastuzumab in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Pazopanib in Combination with Lapatinib or Trastuzumab
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combinations of pazopanib and either lapatinib or trastuzumab that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.
Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.
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.
Trastuzumab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, your doctor will decide which study drugs you will receive based on the disease type and the drugs you have taken in the past
You will receive either a combination of pazopanib and lapatinib (Arm A) or a combination of pazopanib and trastuzumab (Arm B).
Up to 5 dose levels of each combination will be tested. Up to 6 participants will be enrolled at each dose level of each combination. The first group of participants will receive the lowest dose level of each combination. Each new group(s) will receive a higher combination than the group before it, if no intolerable side effects were seen. Participants may be enrolled on 1-3 similar dose levels at the same time. You will be assigned to a dose level based on when you joined this study. This will continue until the highest tolerable dose(s) of the study drug combination is found.
The dose of the study drug combination that you receive may be lowered if you have intolerable side effects.
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 cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months.
- •Patients must have measurable or evaluable disease.
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status </=
- •Abnormal organ function is permitted; however, patients must have : Plt >/=100,000/, absolute neutrophil count (ANC) >/=1500, total Bilirubin </=2.0 mg/dl, Creatinine </=2.0 mg/dl and Prothrombin Time/International Normalized Ratio/Partial Thromboplastin Time (PT/INR/PTT) within 1.5 X upper limit of normal (ULN).
- •A woman is eligible to enter and participate in the study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, bilateral oophorectomy (ovariectomy), bilateral tubal ligation, is post-menopausal (total cessation of menses for ≥ 1 year); OR if of childbearing potential, has a negative serum pregnancy test at screening, and agrees to use adequate contraception.
- •A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.
- •Signed informed consent approved by the Institutional Review Board prior to patient entry.
- •Expanded Cohort only: Patients must have HER2 amplification, HER2 mutation, c-Met amplification, c-Met mutation, EML4-ALK translocation, or epidermal growth factor receptor (EGFR) mutation.
排除标准
- •Poorly-controlled hypertension (systolic blood pressure [SBP] >/= 140 mmHg, or diastolic blood pressure [DBP]>/= 90 mmHg).
- •Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes,congestive cardiac failure )
- •History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1 of treatment period.
- •History of venous or arterial thrombosis within 3 months of Day 1 of treatment Period.
- •Current use of therapeutic warfarin. NOTE: both low molecular weight heparin and prophylactic low-dose warfarin are permitted; however, PT/PTT must meet above inclusion criteria.
- •Excessive risk of bleeding or thrombosis as defined by stroke or severe bleeding within the prior 6 months.
- •Patients who received investigational drugs, chemotherapy or immunotherapy patient must be >/= five half-lives or >/= 3 weeks from the last dose of treatment, whichever is shorter.
- •Any major surgery or radiotherapy within 14 days of treatment.
- •Patients with a documented Left Ventricular Ejection Fraction < 45%.
研究组 & 干预措施
Arm A: Pazopanib + Lapatinib
Oral Pazopanib 200 mg every other day starting on day 1 and oral Lapatinib 500 mg daily starting day 1, both for 28 days.
干预措施: Pazopanib (Drug)
Arm A: Pazopanib + Lapatinib
Oral Pazopanib 200 mg every other day starting on day 1 and oral Lapatinib 500 mg daily starting day 1, both for 28 days.
干预措施: Lapatinib (Drug)
Arm B: Pazopanib + Trastuzumab
Oral Pazopanib 200 mg daily for 28 day cycle and Trastuzumab (Herceptin®) 4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1, with a maintenance dose of 2 mg/kg every week as 30 minute infusion by vein.
干预措施: Trastuzumab (Herceptin®) (Drug)
Arm B: Pazopanib + Trastuzumab
Oral Pazopanib 200 mg daily for 28 day cycle and Trastuzumab (Herceptin®) 4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1, with a maintenance dose of 2 mg/kg every week as 30 minute infusion by vein.
干预措施: Pazopanib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Pazopanib in Combination with Lapatinib or Trastuzumab
时间窗: 28 day cycle
MTD is defined as highest dose in which incidence of dose limiting toxicity (DLT) was less than 33% (approximately two or more participants in a dose cohort).
Tumor Response
时间窗: End of second 28 day cycle
Computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, positron emission tomography (PET) scan, and/or x-ray to check the status of the disease. Tumor response calculated by Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization Working Group (WHO) criteria. A tumor response is defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% or (4) a partial response according to the Choi criteria.
次要结局
未报告次要终点