• 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 ]

• Tumor response as assessed by radiological measurements every 8 weeks
• Pharmacokinetic profile and pharmacokinetic effects assessed before beginning treatment, every 8 weeks during treatment, and after completion of study treatment
• Antiproliferative and apoptic effects as assessed by radiological measurements every 8 weeks
• 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
• Antiangiogenic effects on tumor samples from treated patients every 8 weeks
• Histone acetylation in peripheral blood mononuclear cells before beginning treatment, every 8 weeks during treatment, and after completion of study treatment
• Adverse events and changes in laboratory parameters every 8 weeks

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.

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.

• Lymphoma
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

• Drug: entinostat
• Drug: isotretinoin

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