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

NCT ID: NCT00098891

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

entinostat

Intervention Type: DRUG

Given orally

isotretinoin

Intervention Type: DRUG

Given orally

Interventions

entinostat

Given orally

Intervention Type: DRUG

isotretinoin

Given orally

Intervention Type: DRUG

Other Intervention Names

HDAC inhibitor SNDX-275; SNDX-275; 13-CRA; Amnesteem; Cistane; Claravis; Sotret

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Pili

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

JHOC-J0438

Identifier Type: -

Identifier Source: secondary_id

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000396776

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02634

Identifier Type: -

Identifier Source: org_study_id