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MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
This study has been completed.

First Received on December 8, 2004.   Last Updated on March 13, 2010   History of Changes
Sponsor: Sidney Kimmel Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00098891
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: entinostat
Drug: isotretinoin
Phase I

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,196), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity and maximum tolerated dose as assessed by radiological measurements every 8 weeks [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response as assessed by radiological measurements every 8 weeks [ Designated as safety issue: No ]
  • Pharmacokinetic profile and pharmacokinetic effects assessed before beginning treatment, every 8 weeks during treatment, and after completion of study treatment [ Designated as safety issue: No ]
  • Antiproliferative and apoptic effects as assessed by radiological measurements every 8 weeks [ Designated as safety issue: No ]
  • Methylation status and expression of retinoic acid receptor beta (RAR-B) as assessed by descriptive statistics before beginning treatment, every 8 weeks during treatment, and after completion of study treatment [ Designated as safety issue: No ]
  • Antiangiogenic effects on tumor samples from treated patients every 8 weeks [ Designated as safety issue: No ]
  • Histone acetylation in peripheral blood mononuclear cells before beginning treatment, every 8 weeks during treatment, and after completion of study treatment [ Designated as safety issue: No ]
  • Adverse events and changes in laboratory parameters every 8 weeks [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: December 2004
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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

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

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor or lymphoma

    • Metastatic, progressive, refractory, or unresectable disease
    • Not amenable to standard curative measures
  • No known brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • Hemoglobin > 9 g/dL

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • No suspected Gilbert's syndrome

Renal

  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No unstable cardiac arryhthmia

Gastrointestinal

  • Able to take and retain oral medications
  • No malabsorption problems
  • No acute or chronic gastrointestinal condition

Other

  • Not pregnant or nursing
  • Negative pregnanct 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • 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

Chemotherapy

  • 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

Endocrine therapy

  • 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

Radiotherapy

  • More than 4 weeks since prior anticancer radiotherapy
  • More than 2 weeks since prior palliative radiotherapy
  • No concurrent anticancer radiotherapy

Surgery

  • More than 4 weeks since prior major surgery

Other

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098891

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Roberto Pili, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00098891     History of Changes
Other Study ID Numbers: CDR0000396776, JHOC-J0438, NCI-6798, JHOC-04060103
Study First Received: December 8, 2004
Last Updated: March 13, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
primary central nervous system non-Hodgkin lymphoma
intraocular lymphoma
small intestine lymphoma
recurrent adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
stage IV grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
stage IV grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage IV marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Intestinal Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases
Isotretinoin
Histone Deacetylase Inhibitors
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012