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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: 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: entinostat (Drug); isotretinoin (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Roberto Pili, Principal Investigator, Affiliation: Johns Hopkins University

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

Clinical Details

Official title: 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.

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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

Maximum tolerated dose of entinostat and isotretinoin in combination

Secondary outcome:

Pharmacokinetics

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

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Johns Hopkins University, Baltimore, Maryland 21287-8936, United States
Additional Information

Starting date: October 2004
Last updated: January 23, 2013

Page last updated: August 23, 2015

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