A Phase I Study of the CDK4/6 Inhibitor PD-0332991, 5-Fluorouracil, and Oxaliplatin in Patients With Advanced Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 dose and schedule
研究概览
简要总结
This study is for patients with advanced solid tumor malignancies (cancer that has spread to other parts of the body).
The purpose of this study is to test the safety and effectiveness of a new combination of drugs, PD-0332991 and 5-Fluorouracil and Oxaliplatin for patients with advanced solid tumor malignancies . PD-0332991 stops cells from dividing by blocking an enzyme called cyclin-dependent kinase (CDK), which cancer cells need to grow and divide. By inhibiting this enzyme, PD-0332991 prevent cancer cells from growing and dividing, while the 5-Fluorouracil and Oxaliplatin damage the cells, hopefully increasing the killing of cancer cells, thus decreasing the tumors in the body.
PD-0332991 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration for use in colorectal cancer. It is given as a pill which is taken once a day for one week followed by one week off. 5-Fluorouracil and Oxaliplatin are administered as an infusion into a vein once every 2 weeks and are approved for and used as chemotherapy for several cancers.
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
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Retinoblastoma-positive, histologically proven advanced solid tumor malignancies for which no curative therapy exists
- •Biopsy accessible tumor deposits
- •Corrected QT interval less than 500 milliseconds by EKG
- •ECOG preformance status 0-2
- •Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease and have not had treatment with steroids within 1 week of study enrollment.
- •Adequate hepatic, bone marrow, and renal function
- •Partial thromboplastin time must be </= 1.5 x upper limit normal range and INR < 1.
- •Subjects on anticoagulant will be permitted to enroll as long as the INR is in acceptable therapeutic range.
- •Life expectancy > 12 weeks
- •Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months.
- •Subject is capable of understanding and complying with parameters of the protocol and able to sign and date the informed consent.
排除标准
- •Intolerant of, or ineligible for 5-FU, oxaliplatin and/or the combination of both
- •CNS metastases that do not meet the criteria outlined in the inclusion criteria
- •Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1 with neuropathic pain
- •Active severe infection or known chronic infection with HIV or hepatitis B virus
- •Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia or myocardial infarction, stroke, or congestive heart failure within the last 6 months.
- •Life-threatening visceral disease or other severe concurrent disease
- •Women who are pregnant or breastfeeding
- •Anticipated patient survival under 3 months
- •Concurrent use of known CYP 3A4 inhibiting or activating medications
- •Clinically significant and uncontrolled major medical condition(s)
研究组 & 干预措施
PD-0332991, 5-FU and oxaliplatin
PD-0332991 with 5-FU and oxaliplatin
干预措施: PD-0332991 (Drug)
PD-0332991, 5-FU and oxaliplatin
PD-0332991 with 5-FU and oxaliplatin
干预措施: 5-FU (Drug)
PD-0332991, 5-FU and oxaliplatin
PD-0332991 with 5-FU and oxaliplatin
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Recommended Phase 2 dose and schedule
时间窗: 18 months
The dose and schedule of PD-0332991 to be used in combination with 5-FU
次要结局
- Toxicity of the combination of PD-0332991, 5-FU, and oxaliplatin(18 months)
- Pharmacodynamics(18 months)
- Response rate(18 months)
- Disease control rate(4 months)
- Trough level of PD-0332991 on Day 1 of Cycles 1-4(4 months)