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

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.

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