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CompletedNCT00098891Updated Jan 24, 2013

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

A Phase 1 interventional study of entinostat and isotretinoin in Adult Grade III Lymphomatoid Granulomatosis, Anaplastic Large Cell Lymphoma and Angioimmunoblastic T-cell Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-01-24.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
24
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • 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
03

In context

Burkitt Lymphoma

392 studies on the registry are indexed under Burkitt Lymphoma; 114 are open to participants now.

This study's enrollment of 24 is below the median of 41 across 354 interventional studies indexed under Burkitt Lymphoma.

Browse Burkitt Lymphoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
24 participants (actual)

Study arms

  • 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 · Drug: isotretinoin

Interventions

  • Drugentinostat

    Given orally

    Also known as: HDAC inhibitor SNDX-275, SNDX-275

  • Drugisotretinoin

    Given orally

    Also known as: 13-CRA, Amnesteem, Cistane, Claravis, Sotret

06

What researchers measure

Primary outcomes

  1. Dose limiting toxicities defined as an adverse event which is likely related to the study medication

    Graded using the CTCAE version 3.0.

    Time frame: 28 days

  2. Maximum tolerated dose of entinostat and isotretinoin in combination

    Time frame: 28 days

Secondary outcomes

  1. Pharmacokinetics

    Time frame: Up to day 21 of course 2

  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

    Graded using the CTCAE version 3.0. Summarized by dose level.

    Time frame: Up to 30 days after completion of study treatment

07

Study locations

1 site
  • Johns Hopkins University
    Baltimore, Maryland 21287-8936, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 24, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00098891
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Dec 9, 2004
Start date
Oct 2004
Primary completion
Mar 2008
Last update
Jan 24, 2013

Study contacts

Roberto Pili
principal investigator · Johns Hopkins University
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2013. You cannot join it, but the record below documents what was studied.

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