MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

January 23, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.

Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when administered with isotretinoin in patients with metastatic, progressive, refractory, or unresectable solid tumors or lymphomas.

SECONDARY OBJECTIVES:

I. Determine, preliminarily, tumor response in patients treated with this regimen.

II. Determine the pharmacokinetic profile of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of MS-275.

Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at the MTD.

Patients are followed monthly.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287-8936
        • Johns Hopkins University

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed solid tumor or lymphoma

    • Metastatic, progressive, refractory, or unresectable disease
    • Not amenable to standard curative measures
  • No known brain metastases
  • Performance status - ECOG 0-2
  • More than 3 months
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • Hemoglobin > 9 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • No suspected Gilbert's syndrome
  • Creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No unstable cardiac arryhthmia
  • Able to take and retain oral medications
  • No malabsorption problems
  • No acute or chronic gastrointestinal condition
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception 1 month before, during, and 3 months after study treatment
  • No known HIV positivity
  • No weight loss > 10% within the past 2 months
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to MS-275 or isotretinoin
  • No other uncontrolled illness
  • No ongoing or active infection
  • No seizure disorder
  • No psychiatric illness or social situation that would preclude study participation
  • More than 4 weeks since prior anticancer vaccine therapy
  • More than 4 weeks since prior anticancer immunotherapy
  • No concurrent anticancer vaccine therapy
  • No concurrent anticancer immunotherapy
  • More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, mitomycin, or other agents known to cause prolonged marrow supression)
  • No concurrent anticancer chemotherapy
  • More than 4 weeks since prior anticancer hormonal therapy except gonadotropin-releasing hormone (GnRH) agonist therapy for non-castrated patients with prostate cancer
  • Concurrent GnRH agonist therapy for non-castrated patients with prostate cancer allowed
  • Concurrent luteinizing hormone-releasing hormone agonist therapy allowed provided there is evidence of tumor progression
  • Concurrent adrenal steroid replacement therapy allowed
  • No concurrent ketoconazole as second-line hormonal treatment for prostate cancer
  • No concurrent corticosteroids except for treatment of refractory nausea or vomiting
  • No other concurrent anticancer hormonal therapy
  • More than 4 weeks since prior anticancer radiotherapy
  • More than 2 weeks since prior palliative radiotherapy
  • No concurrent anticancer radiotherapy
  • More than 4 weeks since prior major surgery
  • Recovered from all prior therapy
  • No prior MS-275

  • No prior oral isotretinoin

    • Isotretinoin for the treatment of acne allowed provided > 3 years since prior administration
  • More than 4 weeks since other prior anticancer therapy
  • No concurrent tetracycline
  • No concurrent high-dose vitamin A
  • No concurrent valproic acid
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (entinostat, isotretinoin)
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Drug: entinostat
Given orally
Other Names:
  • HDAC inhibitor SNDX-275
  • SNDX-275
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities defined as an adverse event which is likely related to the study medication
Time Frame: 28 days
Graded using the CTCAE version 3.0.
28 days
Maximum tolerated dose of entinostat and isotretinoin in combination
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics
Time Frame: Up to day 21 of course 2
Up to day 21 of course 2
Adverse events defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment
Time Frame: Up to 30 days after completion of study treatment
Graded using the CTCAE version 3.0. Summarized by dose level.
Up to 30 days after completion of study treatment

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Roberto Pili, Johns Hopkins University

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 Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

December 8, 2004

First Submitted That Met QC Criteria

December 8, 2004

First Posted (Estimate)

December 9, 2004

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02634
  • U01CA070095 (U.S. NIH Grant/Contract)
  • JHOC-J0438
  • CDR0000396776 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Clinical Trials on entinostat

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Iran

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe