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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00098891
Recruitment Status : Completed
First Posted : December 9, 2004
Last Update Posted : January 24, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE December 8, 2004
First Posted Date  ICMJE December 9, 2004
Last Update Posted Date January 24, 2013
Study Start Date  ICMJE October 2004
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • 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.
  • Maximum tolerated dose of entinostat and isotretinoin in combination [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • Pharmacokinetics [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
Official Title  ICMJE 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.
Brief Summary 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
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Grade III Lymphomatoid Granulomatosis
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Primary Central Nervous System Non-Hodgkin Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Adult T-cell Leukemia/Lymphoma
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Mycosis Fungoides/Sezary Syndrome
  • Stage IV Small Lymphocytic Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Waldenström Macroglobulinemia
Intervention  ICMJE
  • Drug: entinostat
    Given orally
    Other Names:
    • HDAC inhibitor SNDX-275
    • SNDX-275
  • Drug: isotretinoin
    Given orally
    Other Names:
    • 13-CRA
    • Amnesteem
    • Cistane
    • Claravis
    • Sotret
Study Arms  ICMJE 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.
Interventions:
  • Drug: entinostat
  • Drug: isotretinoin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 20, 2007)
24
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00098891
Other Study ID Numbers  ICMJE NCI-2012-02634
JHOC-J0438
U01CA070095 ( U.S. NIH Grant/Contract )
CDR0000396776 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Roberto Pili Johns Hopkins University
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP