A Phase I/II Clinical Trial of Dose-Escalating DHEA in Synovial Sarcoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Progression-free rate (complete response + partial response + stable disease) (Phase II only)
研究概览
简要总结
DHEA is a natural allosteric inhibitor of glucose-6-phosphate dehydrogenase (G6PD). G6PD is a key regulatory enzyme for the survival of synovial sarcoma. The investigators postulate that they can inhibit the production of NADPH in synovial sarcoma and cause cell death by using a naturally occurring G6PD inhibitor.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of histologically or cytologically confirmed metastatic or non-resectable synovial sarcoma.
- •Failed at least one line of chemotherapy. Neoadjuvant and adjuvant chemotherapy count as a prior line of therapy.
- •Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- •At least 16 years of age.
- •ECOG performance status ≤ 2
- •Normal bone marrow and organ function as defined below:
- •Leukocytes ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcl
- •Platelets ≥ 50,000/mcl
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- •Creatinine ≤ IULN OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- •Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Patients using antiestrogens for oral birth control are ineligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- •Currently receiving any other investigational agents.
- •Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DHEA or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- •Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with DHEA. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- •Known mania-associated psychiatric disorder.
- •Known seizure disorder.
- •Using corticosteroids or estrogen-based oral birth control.
- •Using drugs known to lower or increase levels of DHEA.
- •Requires estrogen or testosterone.
- •Taking warfarin sodium. Patients on other blood thinners should be monitored for thrombocytopenia.
- •Taking a strong inhibitor or inducer of cytochrome P
- •Intermediate inhibitors are allowed if deemed medically necessary.
研究组 & 干预措施
Arm 1: DHEA Dose Level 1
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: DHEA (Drug)
Arm 1: DHEA Dose Level 1
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: FACT-67 validated survey (Other)
Arm 2: DHEA Dose Level 2
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: DHEA (Drug)
Arm 2: DHEA Dose Level 2
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: FACT-67 validated survey (Other)
Arm 3: DHEA Dose Level 3
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: DHEA (Drug)
Arm 3: DHEA Dose Level 3
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: FACT-67 validated survey (Other)
Arm 4: DHEA Phase II
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: DHEA (Drug)
Arm 4: DHEA Phase II
-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
干预措施: FACT-67 validated survey (Other)
结局指标
主要结局
Progression-free rate (complete response + partial response + stable disease) (Phase II only)
时间窗: Up to 5 years
* Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction inf short axis to \<10mm, disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diaters while on study
Maximum tolerated dose (MTD) of DHEA (Phase I only)
时间窗: Completion of cycle 1 for all phase I patients (estimated to be 2 years)
* MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached. * Dose-limiting toxicities are defined as one of the following events occurring during the 1st cycle of treatment thought to be possibly, probably, or definitely related to treatment: * Grade 3 or greater liver function test abnormalities * Grade 3 or greater psychiatric disorder * Quality of life (QOL) alteration (change in score of 30%)
次要结局
- Rate of progression-free survival (PFS) (Phase II only)(3 months)
- Toxicity of DHEA as measured by grade and frequency of adverse events(30 days after completion of treatment (estimated to be 7 months))