A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities defined as an adverse event which is likely related to the study medication
研究概览
简要总结
Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells
详细描述
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when administered with isotretinoin in patients with metastatic, progressive, refractory, or unresectable solid tumors or lymphomas.
SECONDARY OBJECTIVES:
I. Determine, preliminarily, tumor response in patients treated with this regimen.
II. Determine the pharmacokinetic profile of this regimen in these patients.
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
- •Histologically confirmed solid tumor or lymphoma
- •Metastatic, progressive, refractory, or unresectable disease
- •Not amenable to standard curative measures
- •No known brain metastases
- •Performance status - ECOG 0-2
- •More than 3 months
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •WBC ≥ 3,000/mm^3
- •Hemoglobin > 9 g/dL
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •No suspected Gilbert's syndrome
- •Creatinine ≤ 1.5 times ULN
- •Creatinine clearance ≥ 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No unstable cardiac arryhthmia
- •Able to take and retain oral medications
- •No malabsorption problems
- •No acute or chronic gastrointestinal condition
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-method contraception 1 month before, during, and 3 months after study treatment
- •No known HIV positivity
- •No weight loss > 10% within the past 2 months
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to MS-275 or isotretinoin
- •No other uncontrolled illness
- •No ongoing or active infection
- •No seizure disorder
- •No psychiatric illness or social situation that would preclude study participation
- •More than 4 weeks since prior anticancer vaccine therapy
- •More than 4 weeks since prior anticancer immunotherapy
- •No concurrent anticancer vaccine therapy
- •No concurrent anticancer immunotherapy
- •More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, mitomycin, or other agents known to cause prolonged marrow supression)
- •No concurrent anticancer chemotherapy
- •More than 4 weeks since prior anticancer hormonal therapy except gonadotropin-releasing hormone (GnRH) agonist therapy for non-castrated patients with prostate cancer
- •Concurrent GnRH agonist therapy for non-castrated patients with prostate cancer allowed
- •Concurrent luteinizing hormone-releasing hormone agonist therapy allowed provided there is evidence of tumor progression
- •Concurrent adrenal steroid replacement therapy allowed
- •No concurrent ketoconazole as second-line hormonal treatment for prostate cancer
- •No concurrent corticosteroids except for treatment of refractory nausea or vomiting
- •No other concurrent anticancer hormonal therapy
- •More than 4 weeks since prior anticancer radiotherapy
- •More than 2 weeks since prior palliative radiotherapy
- •No concurrent anticancer radiotherapy
- •More than 4 weeks since prior major surgery
- •Recovered from all prior therapy
- •No prior MS-275
- 另有 8 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (entinostat, isotretinoin)
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: entinostat (Drug)
Treatment (entinostat, isotretinoin)
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: isotretinoin (Drug)
结局指标
主要结局
Dose limiting toxicities defined as an adverse event which is likely related to the study medication
时间窗: 28 days
Graded using the CTCAE version 3.0.
Maximum tolerated dose of entinostat and isotretinoin in combination
时间窗: 28 days
次要结局
- Pharmacokinetics(Up to day 21 of course 2)
- Adverse events defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment(Up to 30 days after completion of study treatment)