Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin
研究概览
简要总结
This phase I trial studies the side effects and best dose of temsirolimus and metformin hydrochloride in treating patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced or metastatic). Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Metformin hydrochloride is a drug used to treat diabetes that may also prevent or slow the growth of cancers. Giving temsirolimus and metformin hydrochloride together may kill more tumor cells.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of temsirolimus and metformin based on when you join this study. Up to 6 dose levels of temsirolimus and metformin will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of temsirolimus and metformin is found.
Expansion Groups:
When the highest tolerable dose of the study drug combination is found, there will be one group of up to 40 endometrial carcinoma patients enrolled in a tumor-specific expansion group.
Study Drug Administration:
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
- 14 Years 至 —（Child, 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 therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
- •Patients must have evaluable or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •Patients must be >= 4 weeks beyond treatment of any chemotherapy, other investigational therapy, hormonal, biological, targeted agents or radiotherapy, and must have recovered to =< grade 1 or previous baseline for each toxicity; exception: patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field; patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 weeks (wks), whichever is shorter, from the last day of treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotropin-releasing hormone [GnRH] agonist), ovarian, or breast cancer are not exclusionary
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Absolute neutrophil count >= 1000/mL
- •Platelets >= 75,000/mL
- •Creatinine < 1.5 mg/dl in males and < 1.4 in females
- •T. Bilirubin </= 1.5 X ULN
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X ULN (=< 5 X ULN for patients with liver and/or bone metastases)
- •Women of child-bearing potential MUST have a negative serum or urine pregnancy test unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity); patients should not become pregnant or breastfeed while on this study; sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose
- •Ability to understand and willingness to sign a written informed consent document
- •Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies
排除标准
- •Patients who are pregnant or breastfeeding
- •Uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization
- •History of hypersensitivity to temsirolimus or metformin
- •History of cerebral vascular accident (CVA), myocardial infarction or unstable angina within the previous six months before starting therapy
- •New York Heart Association class III or greater congestive heart failure
- •Patients with major surgery within 30 days prior to entering the study
- •Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs
- •Patients on drugs that are strong cytochrome P450, family 3, subfamily A, polypeptide 4 (P450 CYP3A4) modifiers; these drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus; the strong inducing or inhibiting agents should not restart until 1 week after the end of the study treatment; NOTE: we will allow replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy
- •Patients with a history of any grade of persistent or chronic nausea or vomiting within the last 4 weeks related to prior therapy or disease process
研究组 & 干预措施
Temsirolimus + Metformin
Starting dose of Temsirolimus 25 mg by vein weekly. Metformin titrated over 3 weeks at 500 mg by mouth daily. Four weeks of treatment constitute 1 cycle. Cycle one (1) however, will be 6 weeks long to allow for metformin titration.
干预措施: Temsirolimus (Drug)
Temsirolimus + Metformin
Starting dose of Temsirolimus 25 mg by vein weekly. Metformin titrated over 3 weeks at 500 mg by mouth daily. Four weeks of treatment constitute 1 cycle. Cycle one (1) however, will be 6 weeks long to allow for metformin titration.
干预措施: Metformin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin
时间窗: 10 weeks
MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. DLTs defined as adverse events (AEs) related to study agents which occur during first cycle of treatment. Toxicity must have possible, probable or definite attribution to study drugs.
次要结局
- Clinical Tumor Response(10 weeks)