Vorinostat in Treating Patients With Kidney Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well vorinostat works in treating patients with advanced kidney cancer. 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. Vorinostat may also stop the growth of tumor cells by blocking blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the antitumor activity of vorinostat (SAHA), in terms of objective response and progression rate, in patients with advanced renal cell carcinoma. SECONDARY OBJECTIVES: I. Evaluate the safety and tolerability of this drug, in terms of toxicity profile, in these patients. II. Evaluate overall survival, progression-free survival, and survival rate at 12 months in patients treated with this drug. III. Correlate changes in biologic measurements with outcomes of patients treated with this drug. OUTLINE: This is an open-label, multicenter study. Patients receive oral vorinostat (SAHA) twice daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may have the option of continuing treatment beyond 52 weeks at the discretion of the investigator. After completion of study treatment, patients are followed within 1 month and then approximately every 2 months thereafter.

Official Title
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A Phase II, Pharmacokinetic and Biologic Correlative Study of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Advanced Renal Cell Carcinoma (RCC)

Conditions
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Recurrent Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: Vorinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma that is either metastatic or inoperable Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Disease is recurrent or refractory to interleukin-2 (IL-2) or interferon-based therapy OR new diagnosis in previously untreated patients who are not appropriate candidates to receive IL-2 based treatment Patients who have failed up to 4 lines of prior immunotherapy or biological therapy allowed No known brain metastases or leptomeningeal disease Stable brain metastases or curatively resected brain metastases without neurologic dysfunction for ≥ 6 months allowed ECOG performance status 0-2 OR Karnofsky 70-100% Life expectancy ≥ 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 50 mL/min Total bilirubin within normal limits AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present) No history of active malignancy (other than renal cell carcinoma) within the past 3 years other than nonmelanomatous skin cancer, in situ breast cancer, or in situ cervical cancer No history of allergic reactions to compounds of similar chemical or biological composition to vorinostat (SAHA) No uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia No psychiatric illness or social situation that would preclude study compliance No clinically significant hypercalcemia No significant traumatic injury within the past 21 days Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No gastrointestinal disease resulting in an inability to take oral medication No requirement for IV alimentation No active peptic ulcer disease Recovered from prior therapy Prior nephrectomy or resection of metastatic lesions allowed provided full surgical recovery has occurred No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin) No radiotherapy within the past 4 weeks No valproic acid for at least 2 weeks prior to study enrollment No prior surgical procedures affecting absorption No major surgery within the past 21 days No concurrent antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy

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: Arm I<br>Patients receive oral vorinostat (SAHA) twice daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may have the option of continuing treatment beyond 52 weeks at the discretion of the investigator. | Drug: Vorinostat<br>* Given orally<br>* Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Objective response is measured using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST criteria. Complete Response (CR) - Disappearance of all target lesions, Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival |  | 1 year | 
| Overall Survival (OS) and Median OS |  | 1 year | 
| Safety and Tolerability |  | 1 year |