Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Tretinoin and Interleukin-2 in Treating Patients With Stage IV Kidney Cancer

Basic Trial Information

Objectives

Primary

1. 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.
2. 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

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

Entry 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

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
• Prior adjuvant therapy allowed
  • Study therapy is not to be used as adjuvant therapy for completely resected late (> 1 year until identification) solitary site of disease metastasis or non-metastatic disease
• No prior participation in this clinical study
• At least 60 days since other prior anticancer drugs
• Concurrent seizure medication allowed

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

• None of the following cardiovascular conditions within the past year:
  • Uncontrolled hypertension
  • Myocardial infarction
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Class II-IV peripheral vascular disease within the past year
  • 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

Expected Enrollment

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

Outcomes

Ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment
In vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment

Frequency of treatment-related side effects
Clinical objective response
Progression-free survival
Correlation of DC:ImC ratio with clinical objective response
Correlation of the extent of change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels

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.

Mirza N, Fishman M, Fricke I, et al.: All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66 (18): 9299-307, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Mayer Fishman, MD, PhD, Protocol chair		Ph: 813-745-8311; 888-663-3488 Email: mayer.fishman@moffitt.org

Registry Information
Official Title		Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer
Trial Start Date		2004-08-19
Registered in ClinicalTrials.gov		NCT00100906
Date Submitted to PDQ		2004-11-17
Information Last Verified		2007-02-16
NCI Grant/Contract Number		CA76292, CA101324

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