MS-275 In Treating Patients With Advanced Solid Tumors Or Lymphoma

Study Overview

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.

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.

Cancer

DRUG: entinostat

010124
01-C-0124
NCI-2792
CDR0000068615

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2001-07-11	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-03-14
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-03-15
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2012-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
N/A

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Dose-limiting toxicities and maximum tolerated dose
Pharmacology and pharmacokinetics

Secondary Outcome Measures	Measure Description	Time Frame
Acetylation of histones in peripheral blood
Tumor response by CT scan every 12 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

18 and over

ECOG 0-2 OR
Karnofsky 50-100%

More than 3 months

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

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

At least 4 weeks since prior anticancer vaccine therapy and recovered
No concurrent immunotherapy

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

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

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

At least 3 weeks since prior major surgery

No other concurrent investigational or commercial antineoplastic therapies

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Shivaani Kummar, MD, NCI - Medical Oncology Branch

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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Clinical Trial Record