Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as vorinostat and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and capecitabine in treating patients with unresectable or metastatic solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and recommended phase II dose of vorinostat (SAHA) and capecitabine in patients with metastatic or unresectable solid tumors. Determine the safety and tolerability of this regimen in these patients. Secondary Correlate the clinical effects with the pharmacokinetic effects of this regimen in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients receive oral vorinostat (SAHA) once or twice daily and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of CR. Patients achieving a partial response receive 2 courses beyond documentation of best response. Cohorts of 3-6 patients receive escalating doses of SAHA and capecitabine 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. An additional 12 patients are treated at the MTD. After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter. PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study within 6-10 months.

Official Title
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A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: capecitabine
* Drug: vorinostat


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant solid tumor Metastatic or unresectable disease Standard curative or palliative measures do not exist or are no longer effective Patients who received prior radiotherapy must have measurable disease outside a previously irradiated field OR disease progression after prior radiotherapy 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 normal (ULN) Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to swallow oral medication No clinical or radiological diagnosis of bowel obstruction No ongoing or active infection No history of allergic reaction attributed to compounds of similar chemical or biological composition to suberoylanilide hydroxamic acid or other agents used in this study No known dihydropyrimidine dehydrogenase deficiency No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior fluorouracil allowed No prior capecitabine Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy and recovered No prior radiotherapy to > 40% of bone marrow Surgery At least 4 weeks since prior surgery and recovered Other At least 2 weeks since prior valproic acid No other concurrent investigational agents No other concurrent anticancer therapy No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAHA (Suberoylanilide Acid) with Capecitabine<br> | Drug: capecitabine<br> <br> Drug: vorinostat<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated doses of vorinostat (SAHA) and capecitabine |  | 1 cycle | 
| Safety and tolerability as assessed by CTCAE v3.0 |  | All cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as assessed by RECIST criteria |  | Every 2 cycles | 
| Molecular markers as assessed by molecular analysis |  | Cycle 1 | 
| Survival |  | progression free survival every 2 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific