• Pharmacokinetics at course 1 and 2 [ Designated as safety issue: No ]
• Anti-tumor activity by tumor measurements using the RECIST criteria at courses 1 and 2 [ Designated as safety issue: No ]
• Toxicity at course 1 and 2 [ Designated as safety issue: Yes ]

• Pharmacokinetics at course 1 and 2
• Anti-tumor activity by tumor measurements using the RECIST criteria at courses 1 and 2
• Toxicity at course 1 and 2

RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and bortezomib in treating patients with metastatic or unresectable solid tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of vorinostat (SAHA) and bortezomib in patients with metastatic or unresectable solid tumors.

Secondary

• Determine the pharmacokinetics and antitumor activity of this regimen in these patients.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral vorinostat (SAHA) twice daily on days 1-14 in step A. Patients receive oral vorinostat (SAHA) twice daily on days 1-4 and 8-11 in Step B and bortezomib IV over 3-5 seconds on days 2, 5, 9, and 12 during the first course and on days 1, 4, 8, and 11 during subsequent courses in both steps A and B. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of bortezomib 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 6 additional patients receive bortezomib at the MTD. Subsequent cohorts of 3-6 patients receive escalating doses of SAHA until the MTD of that drug is determined.

PROJECTED ACCRUAL: A total of 3-66 patients will be accrued for this study within 14 months.

• Drug: bortezomib
• Drug: vorinostat

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy

  • Metastatic or unresectable disease
• Standard curative or palliative measures do not exist OR are no longer effective
• Measurable or evaluable disease
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No history of myocardial infarction
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No severe pulmonary disease requiring oxygen

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 28 days after study participation
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs or agents
• No pre-existing neuropathy ≥ grade 2
• No uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to > 25% of bone marrow
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• At least 2 weeks since prior valproic acid
• No prior bortezomib
• No concurrent enzyme-inducing anticonvulsant agents
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy