Vorinostat in Treating Patients With Kidney Cancer

Phase 2

Completed

Conditions: Recurrent Renal Cell Carcinoma
Stage IV Renal Cell Cancer

Interventions: Drug: Vorinostat

Registration Number: NCT00278395

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	Vorinostat	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.

Primary Outcome Measures

Name	Time	Method
Objective Response	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	1 year
Safety and Tolerability	1 year
Overall Survival (OS) and Median OS	1 year

Trial Locations

Locations (2): Institute for Drug Development
🇺🇸
San Antonio, Texas, United States
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States