Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer
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Purpose
This phase I/II trial is studying the side effects and best dose of isotretinoin when given together with vorinostat and to see how well they work in treating patients with advanced kidney cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may cause kidney cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may kill more tumor cells.
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Renal Cell Cancer Stage III Renal Cell Cancer Stage IV Renal Cell Cancer |
Drug: vorinostat Drug: isotretinoin Other: pharmacological study Other: laboratory biomarker analysis |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Combination With Isotretinoin (13-cis Retinoic Acid, 13-CRA) in the Treatment of Patients With Advanced Renal Cell Carcinoma |
- Dose limiting and other toxicities associated with vorinostat concurrently administered with isotretinoin [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]Defined as the occurrence of one or more of the following toxicities as graded by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- Maximum tolerated dose of isotretinoin and vorinostat administered in combination [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]Graded using the NCI CTCAE version 3.0.
- Objective response rate of patients with advanced renal cell carcinoma treated with isotretinoin and vorinostat administered in combination [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
- Pharmacokinetics [ Time Frame: At weeks 1 and 5 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 50 |
| Study Start Date: | March 2006 |
| Estimated Primary Completion Date: | January 2100 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (enzyme inhibitor)
Patients receive oral vorinostat (SAHA) twice daily and oral isotretinoin twice daily on days 3-5, 10-12, 17-19, and 24-26. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
|
Drug: vorinostat
Given orally
Other Names:
Drug: isotretinoin
Given orally
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and phase II dose of isotretinoin when given in combination with vorinostat (SAHA) in patients with advanced renal cell carcinoma. (Phase I) II. Define dose-limiting and other toxicities in patients treated with this regimen. (Phase I) III. Determine the objective response rate of patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Conduct a pharmacokinetic analysis of this regimen in these patients. (Phase I) II. Conduct gene profiling analysis of pre-study, paraffin-embedded tissues from patients treated with this regimen. (Phase I) III. Conduct correlative studies to identify the effect of SAHA and isotretinoin on RAR-B, LRAT, and STAT1-3 expression. (Phase I)
OUTLINE: This is a multicenter, phase I, dose-escalation study of isotretinoin, followed by a multicenter, phase II, prospective, non-randomized study.
Phase I: Patients receive oral vorinostat (SAHA) twice daily and oral isotretinoin twice daily on days 3-5, 10-12, 17-19, and 24-26. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of isotretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Phase II: Patients receive SAHA as in phase I and isotretinoin as in phase I at the MTD determined in phase I. Tissue and blood samples are obtained for biomarker/laboratory studies in weeks 1 and 4.
Gene profile analysis is conducted on tumor tissue. After completion of study treatment, patients are followed for 12 weeks.
Eligibility| Ages Eligible for Study: | 21 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically or cytologically confirmed renal cell carcinoma
- Advanced or metastatic disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan (phase II only)
Failed ≥ 2 prior treatment regimens, including chemotherapy, immunotherapy (i.e., interleukin or interferon), biological agents (i.e., kinase inhibitors), or combinations thereof
- An overlap between classes of therapies given concurrently will be counted as 2 prior treatment regimens
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 3 months
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT < 2.5 times upper limit of normal
- Creatinine ≤ 2 mg/dL OR creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception for 1 month before, during, and for 1 month after completion of study treatment
- No history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA), isotretinoin, or other agents or components (e.g., parabens) used in this study
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude study compliance
- See Disease Characteristics
- Recovered from prior therapy
- At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
- At least 4 weeks since prior radiotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- At least 6 weeks since prior chemoimmunotherapy
- No concurrent antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy, including radiation, biologic, or chemotherapeutic agents, for renal cell carcinoma or other tumors
- No other concurrent investigational agents, valproic acid, or other retinoid
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00324740 History of Changes |
| Other Study ID Numbers: | NCI-2009-00095, 0511008257, NYWCCC-0511008257, CDR0000472916, NCI-6896, N01CM62204 |
| Study First Received: | May 10, 2006 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Renal Cell Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Kidney Diseases |
Urologic Diseases Isotretinoin Vorinostat Dermatologic Agents Therapeutic Uses Pharmacologic Actions Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 23, 2013