A Phase I Study of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) in Patients With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable doses of the combinations of lenalidomide and other drugs that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.
详细描述
The Study Drugs:
Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease or prevent the growth of cancer cells.
Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.
Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.
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
- 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
- •Patients with advanced or metastatic cancer that is refractory to standard therapy, has relapsed after standard therapy, or for which there is no standard therapy available.
- •Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, therapeutic radiation, or major surgery. After targeted or biologic therapy there should be 5 half-lives or three weeks, whichever is shorter. Patients may have received palliative localized radiation immediately before or during treatment, providing radiation is not delivered only to the site of disease being treated under this protocol.
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- •Patients must have normal organ and marrow function, defined as absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL (unless these abnormalities are due to bone marrow involvement); creatinine clearance >/= 50 ml/min by Cockcroft-Gault formula; total bilirubin </= 2.0; and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase(SGPT) </= 5 X upper limit of normal (ULN) (unless patient has liver metastases).
- •All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International unit (mIU)/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- •Patients must be able to understand and be willing to sign a written informed consent document.
- •Must be >/= 18 years of age.
排除标准
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- •Use of any other experimental drug or therapy within 21 days of baseline.
- •Known hypersensitivity to thalidomide.
- •History of hypersensitivity to any component of the formulation.
- •The development of erythema nodosum, if characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Patients unwilling or unable to sign informed consent document.
- •Uncontrolled systemic vascular hypertension (Systolic blood pressure >140 mmHg, diastolic blood pressure > 90 mmHg on medication) for patients treated in the bevacizumab or sorafenib arms.
- •Patients with active deep venous thrombosis or pulmonary embolism or patients receiving anti-coagulation.
- •Patients with clinically significant cardiovascular disease: History of cerebro-vascular accident (CVA) within 6 months; Myocardial infarction or unstable angina within 6 months; Unstable angina pectoris.
- •Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 of protocol treatment.
- •Patients that are taking CYP3A4 inducers and/or inhibitors, being considered for the temsirolimus arm: If a patient has a history of taking CYP3A4 inducers and/or inhibitors prior to enrollment on the temsirolimus arm, it is strongly recommended that the patient stops the drug and waits at least 5 half-lives of said drug before initiating therapy on the temsirolimus arm.
研究组 & 干预措施
Lenalidomide + Bevacizumab
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Bevacizumab starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.
干预措施: Lenalidomide (Drug)
Lenalidomide + Bevacizumab
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Bevacizumab starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.
干预措施: Bevacizumab (Drug)
Lenalidomide + Sorafenib
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Sorafenib starting dose: 200 mg by mouth daily for 28 a day cycle.
干预措施: Lenalidomide (Drug)
Lenalidomide + Sorafenib
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Sorafenib starting dose: 200 mg by mouth daily for 28 a day cycle.
干预措施: Sorafenib (Drug)
Lenalidomide + Temsirolimus
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Temsirolimus starting dose: 15 mg by vein every week for a 28 day cycle.
干预措施: Lenalidomide (Drug)
Lenalidomide + Temsirolimus
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Temsirolimus starting dose: 15 mg by vein every week for a 28 day cycle.
干预措施: Temsirolimus (Drug)
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
Lenalidomide starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle. Oxaliplatin starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle. Leucovorin 400 mg/m2 by vein on day 1 of a 21 day cycle. 5-fluorouracil 400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
干预措施: Lenalidomide (Drug)
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
Lenalidomide starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle. Oxaliplatin starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle. Leucovorin 400 mg/m2 by vein on day 1 of a 21 day cycle. 5-fluorouracil 400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
干预措施: Oxaliplatin (Drug)
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
Lenalidomide starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle. Oxaliplatin starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle. Leucovorin 400 mg/m2 by vein on day 1 of a 21 day cycle. 5-fluorouracil 400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
干预措施: Leucovorin (Drug)
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
Lenalidomide starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle. Oxaliplatin starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle. Leucovorin 400 mg/m2 by vein on day 1 of a 21 day cycle. 5-fluorouracil 400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
干预措施: 5-fluorouracil (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)
时间窗: First 21/28 day cycle
If more than 33% of patients enrolled in any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of patients in cohort develop DLT, this cohort considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity, as defined in most current version of NCI CTCAE, even if expected and believed related to study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens, or alopecia), any Grade 4 hematologic toxicity lasting at least 7 days or longer, despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting lasting \> 5 days despite maximum anti-nausea regimens and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in NCI CTCAE.
次要结局
- Tumor Response(4 months)