Recurrent Renal Cell Carcinoma, Stage IV Renal Cell Cancer
Conditions
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.
Interventions
DRUGVorinostat
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Progression-free Survival | 1 year |
| Overall Survival (OS) and Median OS | 1 year |
| Safety and Tolerability | 1 year |
Countries
United States
Participant flow
Recruitment details
Open to recruitment on 12/5/2005, closed to recruitment on 3/3/09 at The University of Texas Health Science Center San Antonio at Cancer and Therapy Research Center
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat The dose of vorinostat was 300 mg two times a day on the first 3 days of every week on a 4-week cycle. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Nonevaluable | 1 |
Baseline characteristics
| Characteristic | Vorinostat |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 14 |
| serious Total, serious adverse events | 1 / 14 |
Outcome results
Primary
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.
Time frame: 1 year
Population: The overall duration of response will be estimated using the Kaplan-Meier method for all patients who presented with an objective response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vorinostat | Objective Response | Best Objective Response Rate (ORR) | 4 participants |
| Vorinostat | Objective Response | Progressive Disease | 7 participants |
Secondary
Overall Survival (OS) and Median OS
Time frame: 1 year
Population: Data were not collected
Secondary
Progression-free Survival
Time frame: 1 year
Population: Data were not collected
Secondary
Safety and Tolerability
Time frame: 1 year
Population: Data were not collected