NCT00020579已完成1 期
A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 6
- 主要终点
- Dose-limiting toxicities and maximum tolerated dose
研究概览
简要总结
RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.
详细描述
OBJECTIVES:
- Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 in patients with advanced solid tumors or lymphomas.
- Determine the profile of adverse events, including changes in laboratory parameters, in patients treated with this drug.
- Assess the pharmacology and pharmacokinetics of this drug in these patients.
- Design MS-275 regimens with possibly more frequent dose administration based on the pharmacology of MS-275 using the schedule in this study.
- Determine the antineoplastic activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral MS-275 once on day 1. Courses repeat every 2 weeks (every 2-week schedule). Alternatively, patients receive oral MS-275 once on days 1, 8, 15, and 22 (weekly schedule). Courses repeat every 6 weeks. Treatment for both schedules continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of MS-275 on the every 2-week schedule until the maximum tolerated dose (MTD) is determined. Once the MTD for the every 2-week schedule is determined, patients receive treatment on the weekly schedule as above. The MTD is then determined for the weekly schedule. The MTD for both schedules is defined as the dose preceding that at which at least 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined for the weekly schedule, up to 3 additional patients are accrued to receive MS-275 at the MTD of the weekly schedule.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignancy that is metastatic or unresectable and for which no effective standard curative or palliative therapy exists
- •Brain metastases allowed provided both of the following criteria are met:
- •Received treatment for the brain metastases
- •Stable for ≥ 6 months without steroids or antiseizure medications
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •ECOG 0-2 OR
- •Karnofsky 50-100%
- •Life expectancy:
- •More than 3 months
- •Hematopoietic:
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN) (≤ 3 mg/dL for patients with Gilbert's syndrome)
- •AST/ALT no greater than 2.5 times ULN
- •Albumin at least 75% of lower limit of normal
- •Creatinine normal OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •Cardiac ejection fraction normal by MUGA
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Adequate oral intake
- •No weight loss of more than 10% of actual body weight within the past 2 months
- •No history of allergic reaction to compounds of similar chemical or biological composition to study drug
- •No other uncontrolled illness
- •No ongoing or active infection
- •No seizure disorder
- •No psychiatric illness or social situation that would preclude study compliance
- •No acute or chronic gastrointestinal conditions (e.g., peptic ulcer or colitis) within the past 2 months that would interfere with drug tolerance or absorption
- •Willing and able to self-administer and document doses of MS-275
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 4 weeks since prior anticancer vaccine therapy and recovered
- •No concurrent immunotherapy
- •Chemotherapy:
- •At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •At least 8 weeks since prior UCN-01 and recovered
- •No concurrent chemotherapy
- •Endocrine therapy:
- •At least 4 weeks since prior anticancer hormonal therapy (except gonadotropin-releasing hormone [GnRH] agonists) and recovered
- •Concurrent corticosteroids for physiological replacement, as antiemetic therapy, or for an ongoing condition allowed
- •Must be on a stable dose during the past 4 weeks
- 另有 7 项未显示
排除标准
- 未提供
结局指标
主要结局
Dose-limiting toxicities and maximum tolerated dose
Pharmacology and pharmacokinetics
次要结局
- Acetylation of histones in peripheral blood
- Tumor response by CT scan every 12 weeks
研究者
研究点 (6)
Loading locations...
相似试验
已完成
1 期
MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemiade Novo Myelodysplastic SyndromeRecurrent Adult Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaSecondary Myelodysplastic SyndromeLeukemiaAcute Myeloid LeukemiaMyelodysplastic SyndromeChronic Myelomonocytic LeukemiaNCT00101179National Cancer Institute (NCI)63
已完成
2 期
Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin LymphomaAdult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaNodal Marginal Zone B-cell LymphomaPeripheral T-cell LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaSmall Intestine LymphomaSplenic Marginal Zone LymphomaWaldenstrom MacroglobulinemiaAnaplastic Large Cell LymphomaPost-transplant Lymphoproliferative DisorderNCT01261247Mayo Clinic41
终止
2 期
FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Mantle Cell LymphomaNCT00383565National Cancer Institute (NCI)9
已完成
1 期
MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or LymphomasAdult Grade III Lymphomatoid GranulomatosisAngioimmunoblastic T-cell LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaPrimary Central Nervous System Non-Hodgkin LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaAnaplastic Large Cell LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaSmall Intestine LymphomaSplenic Marginal Zone LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificWaldenström MacroglobulinemiaNCT00098891National Cancer Institute (NCI)24
进行中（未招募）
不适用
Phase II study of MS-275, a histone deacetylase inhibitor, comparing 2 dosage schedules in patients with metastatic melanoma - MS-275 proof of concept in melanomaEUCTR2004-002395-41-DESchering AG100