Expansion Cohort Study of Disulfiram and Chemotherapy in Pancreas Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) (Cohort I)
研究概览
简要总结
This partially randomized phase I trial studies the side effects and best dose of disulfiram when given together with chemotherapy in treating patients with a solid tumor that does not respond to treatment (refractory) or pancreatic cancer that has spread to other places in the body (metastatic) and to compare whether disulfiram and chemotherapy may reduce tumor induced muscle loss. Weight loss occurs in pancreatic cancer patients and is common in a multitude of other cancers. Patients with metastatic cancer and weight loss sometimes are not able to receive treatment due to physical weakness or debility. Disulfiram is a potential inhibitor of muscle degradation and may reduce tumor induced muscle wasting. Disulfiram may also help chemotherapy work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving chemotherapy with or without disulfiram is a better treatment for refractory solid tumors or metastatic pancreatic cancer.
详细描述
PRIMARY OBJECTIVE:
I. To determine the maximally tolerated dose (MTD) of the combination of disulfiram and gemcitabine (gemcitabine hydrochloride) in unresectable solid tumor cancer patients (Cohort 1).
SECONDARY OBJECTIVES:
I. To describe the adverse event profile associated with this combination of disulfiram and chemotherapy (Cohort 2).
II. To describe changes in muscle area at the L3 level from baseline to 28 to 60 days from the baseline computed tomography (CT) scan in patients treated with disulfiram/chemotherapy and with placebo/chemotherapy (Cohort 2).
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
- 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
- •Cohort 1 (dose escalation): histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes
- •Cohort 2 (MTD) only: metastatic adenocarcinoma of the pancreas; prior systemic treatment for metastatic disease is allowed
- •Cohort 2 (MTD) only: Patient is thought to be a short- or long-term candidate for chemotherapy in the opinion of the treating oncologist
- •Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to registration)
- •Platelet >= 100,000/ mm^3 (obtained =< 7 days prior to registration)
- •Total bilirubin =< 2 x upper limit of normal (ULN) (obtained =< 7 days prior to registration)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x ULN (obtained =< 7 days prior to registration)
- •Creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)
- •Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)
- •Cohort 2 (MTD) only: prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN (only if muscle biopsy has not been waived, does not apply to non-Mayo sites that will not be conducting biopsies) (obtained =< 7 days prior to registration)
- •Ability to provide written informed consent
- •Life expectancy >= 12 weeks
- •Cohort 2 (MTD) only: patient willing to undergo muscle biopsies at baseline and after 28 to 35 days of disulfiram/chemotherapy as required by the protocol unless the muscle biopsy has been waived after discussion with the principal investigator (PI); muscle biopsies will not be required at non-Mayo Clinic sites
- •Cohort 2 (MTD) only: patient willing to have paraffin-embedded slides of the primary pancreas tumor or metastatic site, if available, sent to Mayo investigators for this study
- •For women of childbearing potential only: negative urine or serum pregnancy test done =< 7 days prior to registration
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Able to swallow or have medication administered through a gastrostomy tube (G-tube) and absorb the medication
- •Patient willing to complete a medication diary
- •Patient agrees to use acceptable form of contraception during the study and for up to 30 days after last study drug dose if female partner is of childbearing potential
- •Acceptable forms of contraception:
- •Latex condom (always used with spermicide)
- •Diaphragm (always used with spermicide)
- •Cervical cap (always used with spermicide)
- •Acceptable forms of secondary contraception, when used along with a barrier method:
- •Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")
- •Tubal ligation
- •Partner's vasectomy
- •Intrauterine device (non-progesterone T)
- •Vaginal sponge (containing spermicide)
- •Other acceptable forms:
- •100% commitment to abstinence
- •Unacceptable forms of contraception for women of childbearing potential:
- •Oral contraception containing progestins only
- •Intrauterine device (IUD) progesterone T
- •Female condom
- •Natural family planning (rhythm method) or breastfeeding
- •Fertility awareness
- •Withdrawal
- •Cervical shield
排除标准
- •Known standard therapy for the patient's disease that is potentially curative
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, including localized infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
- •Untreated brain metastases
- •Any of the following:
- •Pregnant women
- •Nursing women This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
- •Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Baseline of grade 2 or worse peripheral sensory neuropathy
- •Receiving phenytoin
- •Unable to abstain from alcohol for the duration of the study
研究组 & 干预措施
Cohort I (gemcitabine hydrochloride and disulfiram)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and disulfiram PO on days 1-28 or days 1-35.
干预措施: Disulfiram (Drug)
Cohort I (gemcitabine hydrochloride and disulfiram)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and disulfiram PO on days 1-28 or days 1-35.
干预措施: Gemcitabine Hydrochloride (Drug)
Cohort I (gemcitabine hydrochloride and disulfiram)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and disulfiram PO on days 1-28 or days 1-35.
干预措施: Laboratory Biomarker Analysis (Other)
Cohort II (chemotherapy and disulfiram)
Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35.
干预措施: Chemotherapy (Drug)
Cohort II (chemotherapy and disulfiram)
Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35.
干预措施: Disulfiram (Drug)
Cohort II (chemotherapy and disulfiram)
Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Maximum tolerated dose (MTD) (Cohort I)
时间窗: 28 days
MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients).
次要结局
- Overall survival (OS) (Cohort I and II)(From registration until death due to any cause, assessed up to 3 years)
- Change in muscle area at the L3 level using a computed tomography (CT) scan (Cohort II)(Baseline to day 28)
- Changes in fist-grip strength as measured by hand dynamometer (Cohort II)(Baseline to day 35)
- Response rate (Cohort II)(At 1 month post-treatment)
- Adverse events profile (Cohort I and II)(Up to 30 days post-treatment)
- Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Cohorts I and II)(Up to 30 days post-treatment)
- Change in muscle area at the L3 level using a computed tomography scan (Cohort II)(Baseline to day 35)