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MS-275 in Treating Patients With Advanced Solid Tumors or Lymphoma

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ClinicalTrials.gov Identifier: NCT00020579
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : March 15, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cancer Drug: entinostat Phase 1

Detailed Description:

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.

Disease status is assessed every 3 months.

PROJECTED ACCRUAL: A total of 50-75 patients will be accrued for this study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas
Study Start Date : March 2001
Actual Primary Completion Date : April 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Genetic and Rare Diseases Information Center resources: Stomach Cancer Lymphosarcoma Follicular Lymphoma Renal Cell Carcinoma Esophageal Cancer Ovarian Cancer Fallopian Tube Cancer Vaginal Cancer Ovarian Epithelial Cancer Bile Duct Cancer Anaplastic Astrocytoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Glioma Meningioma Breast Cancer, Male Soft Tissue Sarcoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Osteosarcoma Desmoid Tumor Neuroepithelioma Marginal Zone Lymphoma Carcinoid Tumor Nasopharyngeal Carcinoma Urethral Cancer Mycosis Fungoides Sezary Syndrome Cutaneous T-cell Lymphoma Medulloblastoma Burkitt Lymphoma Leukemia, T-cell, Chronic Adrenocortical Carcinoma Craniopharyngioma Malignant Mesothelioma Gallbladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Laryngeal Cancer Lymphoma, Large-cell Anaplastic Large Cell Lymphoma Kaposi Sarcoma Ewing Sarcoma Ewing's Family of Tumors Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Embryonal Tumor With Multilayered Rosettes Ependymoma Lymphoblastic Lymphoma Testicular Cancer Vulvar Cancer Brain Tumor, Adult Intraocular Melanoma Diffuse Astrocytoma Wilms' Tumor Anal Cancer Primary Liver Cancer Uterine Sarcoma Oligodendroglioma Anaplastic Oligodendroglioma Anaplastic Ependymoma Pineocytoma Parathyroid Carcinoma Adult T-cell Leukemia/lymphoma Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Hemangiopericytoma Supratentorial Primitive Neuroectodermal Tumor Ovarian Germ Cell Tumor Pilocytic Astrocytoma Metastatic Squamous Neck Cancer With Occult Primary Olfactory Neuroblastoma Subependymoma Myxopapillary Ependymoma Midline Lethal Granuloma




Primary Outcome Measures :
  1. Dose-limiting toxicities and maximum tolerated dose
  2. Pharmacology and pharmacokinetics

Secondary Outcome Measures :
  1. Acetylation of histones in peripheral blood
  2. Tumor response by CT scan every 12 weeks


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

Age:

  • 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

Hepatic:

  • 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

Renal:

  • 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

Other:

  • 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
  • No concurrent anticancer hormonal therapy except GnRH agonists for noncastrated patients with prostate cancer

Radiotherapy:

  • At least 4 weeks since prior anticancer radiotherapy and recovered
  • No concurrent radiotherapy

    • Concurrent localized radiotherapy to a single lesion allowed if the patient achieves at least a partial response

Surgery:

  • At least 3 weeks since prior major surgery

Other:

  • No other concurrent investigational or commercial antineoplastic therapies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00020579


Locations
United States, Maryland
National Naval Medical Center
Bethesda, Maryland, United States, 20889-5000
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
Investigators
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch

Publications of Results:
Ryan QC, Headlee D, Sparreboom A, et al.: A phase I trial of an oral histone deacetylase inhibitor, MS-275, in advanced solid tumor and lymphoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-802, 2003.

ClinicalTrials.gov Identifier: NCT00020579     History of Changes
Obsolete Identifiers: NCT00012571
Other Study ID Numbers: 010124
01-C-0124
NCI-2792
CDR0000068615
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: March 15, 2012
Last Verified: March 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent pancreatic cancer
stage III pancreatic cancer
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage III ovarian epithelial cancer
stage III ovarian germ cell tumor
stage IV ovarian epithelial cancer
stage IV ovarian germ cell tumor
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
recurrent cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
fallopian tube cancer
primary peritoneal cavity cancer
recurrent vaginal cancer
stage III vaginal cancer
stage IVA vaginal cancer

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Entinostat
Histone Deacetylase Inhibitors
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action