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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020579
• Other study ID #: 010124
• Secondary ID: 01-C-0124NCI-279
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: March 14, 2012
• Start date: March 2001
• Est. completion date: October 2008

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00012571

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: October 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• entinostat

Locations

Country	Name	City	State
United States	National Naval Medical Center	Bethesda	Maryland
United States	NCI - Center for Cancer Research	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities and maximum tolerated dose			Yes
Primary	Pharmacology and pharmacokinetics			No
Secondary	Acetylation of histones in peripheral blood			No
Secondary	Tumor response by CT scan every 12 weeks			No