Phase I Study of Trientine and Carboplatin in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Carboplatin with Trientine
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 trientine and carboplatin 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:
Trientine is designed to remove excess copper in the body, which may cause cancer cells to stop growing.
Carboplatin is designed to block the growth of cancer cells by stopping cell division, which may cause the cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of carboplatin based on when you joined this study. Up to 3 dose levels of the carboplatin will be tested.
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
- •Patient must have an advanced malignancy that has either failed one or more prior therapies, or for whom there is no established standard of care therapy that prolongs survival by at least 3 months.
- •Only in 1 of 3 expansion cohorts, we will plan to enroll 14 subjects with platinum-resistant malignancy. Patient with platinum-resistant malignancy is defined to have had a treatment-free interval of less than 6 months following a platinum-based regimen.
- •Patient of any age and any gender. However, those who are 12 years old or younger will be eligible after consultation with their pediatric physicians regarding dose initiation and modification of trientine.
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patient is willing to comply with study procedures and follow-up examinations.
- •Patient or primary care taker must be informed of the investigational nature of this study and must sign and give written Institutional Review Board (IRB)-approved informed consent in accordance with institutional guidelines.
- •If patient is of childbearing potential, she or he must agree to practice an effective method of birth control prior to study entry, for the duration of study participation, and for 30 days after the last study dose.
- •Patient has adequate organ functions: serum bilirubin </= 2.0 mg/dL; ALT </= 3 x upper limit of normal (ULN), or ALT </= 5 x ULN if the patient has hepatic metastasis; serum creatinine </= 1.5 mg/dL or a calculated creatinine clearance of at least 60 mL/min.
- •Patient has adequate bone marrow reserve: absolute neutrophil count (ANC) >/= 1,500 /ul, Platelet count >/= 100,000 /ul , and Hemoglobin >/= 9.0 g/dL.
排除标准
- •Patient receiving any concurrent chemotherapy.
- •Underlying medical condition that might be aggravated by treatment or that cannot be controlled, such as active, uncontrolled, serious infection and cardiac dysfunction.
- •Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
- •Known anaphylactic or severe hypersensitivity to study drugs or their analogs.
- •Patient has failed to recover from any prior surgery within 4 weeks of study entry.
- •Patient is pregnant or lactating.
- •Patient has had any treatment specific for tumor control within 3 weeks of dosing with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5 half-lives of biological targeted agents with half-lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents), or failure to recover from the toxic effect of any of these therapies prior to study entry.
- •Patient has any signs of intestinal obstruction interfering with nutrition.
- •Patient has a known history of central nervous system (CNS) metastasis unless the patient has had treatment with surgery or radiation therapy, and is neurologically stable.
- •Patient is not able to swallow oral medication.
- •Patient has clinical evidence of copper deficiency (i.e. ceruloplasmin level was less than 15 mg/dL or free serum copper level less than 2.2 ug/dL).
研究组 & 干预措施
Trientine + Carboplatin MTD Group
Trientine starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group.
干预措施: Trientine (Drug)
Trientine + Carboplatin MTD Group
Trientine starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group.
干预措施: Carboplatin (Drug)
MTD Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group
干预措施: Trientine MTD (Drug)
MTD Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group
干预措施: Carboplatin MTD (Drug)
Carboplatin PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: Trientine MTD (Drug)
Carboplatin PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: Carboplatin MTD (Drug)
Carboplatin PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: PK Testing (Other)
Trientine PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: Trientine MTD (Drug)
Trientine PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: Carboplatin MTD (Drug)
Trientine PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
干预措施: PK Testing (Other)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Carboplatin with Trientine
时间窗: 4 weeks
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (4 weeks). DLT defined as treatment-related grade 3 or greater nonhematological toxicity other than nausea, vomiting, or fatigue.
次要结局
- Treatment Response of Maximum Tolerated Dose (MTD) of Carboplatin with Trientine(After 2, 28 day cycles)