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

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.

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