RATIONALE: Tretinoin may help kidney cancer cells become more like normal cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving tretinoin together with interleukin-2 may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving three different doses of tretinoin together with interleukin-2 works in treating patients with stage IV kidney cancer.

Condition	Treatment or Intervention	Phase
Stage IV Renal Cell Cancer recurrent renal cell cancer renal clear cell carcinoma	Drug: interleukin-2  Drug: tretinoin  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: differentiation therapy  Procedure: interleukin therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment with 3 different doses of tretinoin in patients with stage IV renal cell cancer.
• Assess in vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment with tretinoin and interleukin-2 in these patients.

Secondary

• Determine the frequency of treatment-related side effects in these patients.
• Determine clinical objective response and progression-free survival of patients treated with this regimen.
• Correlate DC:ImC ratio with clinical objective response in patients treated with this regimen.
• Correlate the extent if change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels in these patients.

OUTLINE: This is a randomized, open-label study. Specimens are stratified according to patient prognostic factors, tumor bulk, and extent of dendritic cell to circulating immature cell ratio derangement. Patients are randomized to 1 of 3 tretinoin doses.

Patients receive oral tretinoin three times daily on days 1-7 of week 1. Patients then receive interleukin-2 subcutaneously on days 1-5 of weeks 3-8. Treatment repeats every 10-11 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 2 years.

PROJECTED ACCRUAL: A total of 27-36 patients (9-12 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell cancer
• Stage IV disease
• Histology with clear cell component
• Metastatic OR incompletely resected disease
• Non-measurable disease allowed
• Underwent complete or partial nephrectomy more than 90 days ago
• No unresected primary cancer
• No more than 2 of the following adverse factors:
• Hemoglobin < 10.0 g/dL
• Corrected calcium > upper limit of normal (ULN)
• Lactic dehydrogenase > 1.5 times ULN
• ECOG performance status 2
• Brain metastasis allowed provided more than 90 days of clinical and radiologic stability after the end of its active treatment

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• See Disease Characteristics
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics
• SGOT < 3 times normal
• Bilirubin < 2 times normal

Renal

• See Disease Characteristics
• Creatinine clearance > 40 mL/min

Cardiovascular

• No uncontrolled hypertension
• No myocardial infarction
• No unstable angina
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No class II-IV peripheral vascular disease within the past year
• No other clinically significant cardiovascular disease

Immunologic

• No history of immunodeficiency disease
• No HIV infection
• No ongoing serious infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use two methods of effective contraception during and for 1 month (for women) or 6 months (for men) after study treatment
• Other prior malignancy allowed provided there is no evidence of active disease
• No other medical contraindication to tretinoin or interleukin-2
• No serious non-healing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 60 days since prior immunotherapy

Chemotherapy

• At least 60 days since prior cytotoxic chemotherapy

Endocrine therapy

• See Radiotherapy
• No prior corticosteroids at > physiologic replacement doses for > 3 days within the past 90 days
• Concurrent tamoxifen, toremifene, megestrol, or gonadotropin-releasing hormone agonists allowed
• Concurrent inhaled steroids allowed

Radiotherapy

• More than 7 days since prior external-beam radiotherapy
• No steroid requirement during radiotherapy

Surgery

• See Disease Characteristics
• At least 30 days since other prior debulking surgery

Other

• Prior adjuvant therapy for resected, synchronous stage IV disease allowed
• No prior adjuvant therapy for completely resected late (> 1 year until identification) solitary site of disease metastasis
• No prior adjuvant therapy for non-metastatic disease
• No prior participation in this clinical study
• At least 60 days since other prior anticancer drugs
• Concurrent seizure medication allowed

Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting

Study chairs or principal investigators

Mayer Fishman, MD, PhD,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000407544; MCC-13920; MCC-IRB-102626; NCT00100906
Record last reviewed:  December 2004
Last Updated:  April 5, 2005
Record first received:  January 6, 2005
ClinicalTrials.gov Identifier:  NCT00100906
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08