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NCT Number: NCT00020579

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

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.

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Key information

Conditions

Cancer AIDS-related Kaposi sarcoma Adenocarcinoma Adenoma Adnexal Diseases Adrenal Cortex Diseases Adrenal Cortex Neoplasms Adrenal Gland Diseases Adrenal Gland Neoplasms Adrenocortical Carcinoma Anus Diseases Anus Neoplasms Appendiceal Neoplasms Astrocytoma Bile Duct Diseases Bile Duct Neoplasms Biliary Tract Diseases Biliary Tract Neoplasms Brain Diseases Brain Neoplasms Breast Diseases Breast Neoplasms Breast Neoplasms, Male Bronchial Neoplasms Burkitt Lymphoma Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Carcinoma, Ovarian Epithelial Carcinoma, Renal Cell Carcinoma, Squamous Cell Cecal Diseases Cecal Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Cerebral Ventricle Neoplasms Choroid Plexus Neoplasms Chronic Disease Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Craniopharyngioma DNA Virus Infections Desmoid Tumors Digestive System Diseases Digestive System Neoplasms Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Ependymoma Epstein-Barr Virus Infections Esophageal Diseases Esophageal Neoplasms Esthesioneuroblastoma, Olfactory Eye Diseases Eye Neoplasms Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fibroma Gallbladder Diseases Gallbladder Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Glioma Glioma, Subependymal Gonadal Disorders Head and Neck Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Herpesviridae Infections Hypothalamic Diseases Hypothalamic Neoplasms Immune System Diseases Immunoblastic Lymphadenopathy Immunoproliferative Disorders Infections Intestinal Diseases Intestinal Neoplasms Intraocular Lymphoma Kidney Diseases Kidney Neoplasms Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Lymphadenopathy Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoproliferative Disorders Male Urogenital Diseases Medulloblastoma Melanoma Meningeal Neoplasms Meningioma Mesothelioma Mesothelioma, Malignant Mouth Diseases Mouth Neoplasms Mycosis Fungoides Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Bone Tissue Neoplasms, Complex and Mixed Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Unknown Primary Neoplasms, Vascular Tissue Neoplastic Processes Neoplastic Syndromes, Hereditary Nervous System Diseases Nervous System Neoplasms Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Neuroendocrine Tumors Nevi and Melanomas Olfactory Nerve Diseases Oligodendroglioma Osteosarcoma Ovarian Diseases Ovarian Neoplasms Pancreatic Diseases Pancreatic Neoplasms Parathyroid Diseases Parathyroid Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Penile Diseases Penile Neoplasms Pinealoma Pituitary Diseases Pituitary Neoplasms Pleural Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Prostatic Diseases Prostatic Neoplasms Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Salivary Gland Diseases Salivary Gland Neoplasms Sarcoma Sarcoma, Kaposi Sezary Syndrome Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Squamous Cell Carcinoma of Head and Neck Stomach Diseases Stomach Neoplasms Stomatognathic Diseases Supratentorial Neoplasms Testicular Diseases Testicular Neoplasms Thoracic Neoplasms Thymoma Thymus Neoplasms Tumor Virus Infections Urethral Diseases Urethral Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms Uveal Diseases Uveal Melanoma Uveal Neoplasms Vaginal Diseases Vaginal Neoplasms Virus Diseases Vulvar Diseases Vulvar Neoplasms Wilms Tumor

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

NCI - Center for Cancer Research, Bethesda, Maryland, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Entinostat

Drug

Primary outcomes

  1. Dose-limiting toxicities and maximum tolerated dose

  2. Pharmacology and pharmacokinetics

Secondary outcomes

  1. Acetylation of histones in peripheral blood

  2. Tumor response by CT scan every 12 weeks

Sponsors and collaborators

Lead sponsor

National Institutes of Health Clinical Center (CC)

Nih

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas

Important dates

Study start
2001
Primary completion
2008
Study completion
2008
First posted
Jan 27, 2003
Registry last updated
Mar 15, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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