Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Tretinoin may help kidney cancer cells develop into normal cells. Interferon alfa may interfere with the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of liposomal tretinoin plus interferon alfa in treating patients who have metastatic kidney cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the response in patients with metastatic renal cell carcinoma treated with tretinoin liposome and interferon alfa-2b. Determine the toxicity of this regimen in these patients. Study retinoic acid receptor expression on tissue obtained from selected patients who have tumor biopsies. OUTLINE: This is a dose-escalation study of tretinoin liposome with concurrent individual dose escalation of interferon alfa-2b. (Phase I closed to accrual as of 9/24/03.) Patients receive tretinoin liposome IV over 30 minutes once weekly and interferon alfa-2b subcutaneously on five consecutive days (M-F) for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tretinoin liposome until the maximum tolerated dose (MTD) has been determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined additional patients are accrued and treated at that dose. (Phase I closed to accrual as of 9/24/03.) During the first 3 weeks of the study, patients receive interferon alfa-2b at weekly dose escalations. After week 3, patients continue at the highest acceptable dose level of interferon alfa-2b for the remainder of the study. (Phase I closed to accrual as of 9/24/03.) Patients are followed at 30 days after the last treatment. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued into the phase I portion of this study (Phase I closed to accrual as of 9/24/03). A total of 14-25 patients will be accrued into the phase II portion of this study.

Official Title
-----------------
Phase II Trial of Atragen and Interferon Alfa-2b in Patients With Advanced Renal Cell Carcinoma

Conditions
-----------------
Kidney Cancer

Intervention / Treatment
-----------------
* Biological: recombinant interferon alfa
* Drug: tretinoin liposome


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed metastatic renal cell carcinoma Bidimensionally measurable disease No active brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: More than 3 months Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 No coagulation disorders Hepatic: Bilirubin less than 1.5 mg/dL SGOT and SGPT less than 112.5 IU/L each or less than 2.5 times upper limit of normal No clinically significant hepatic disease, including autoimmune hepatitis Renal: Creatinine less than 2 mg/dL OR Creatinine clearance greater than 50 mL/min No clinically significant renal disease Cardiovascular: No clinically significant cardiac disease No thrombophlebitis Pulmonary: No severe debilitating pulmonary disease No pulmonary embolism Other: No history of diabetes mellitus prone to ketoacidosis No known hypersensitivity to retinoids or retinoic acid derivatives or to interferon or any component of the injection for this study No thyroid abnormalities that hinder maintaining thyroid function at the normal range No severe infection No severe malnutrition No clinically significant retinal abnormalities No pre-existing psychiatric condition, especially depression or a history of severe psychiatric disorder No other concurrent malignancy except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 effective methods of contraception during and for 1 month after study participation PRIOR CONCURRENT THERAPY: Biologic therapy: No more than 1 prior biological response modifier therapy or immunotherapy Chemotherapy: No more than 1 prior chemotherapy regimen Endocrine therapy: No concurrent steroids Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: At least 4 weeks since prior major surgery Other: No prior retinoid therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>Weekly ATRA-IV with recombinant interferon alfa | Biological: recombinant interferon alfa<br> <br> Drug: tretinoin liposome<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response as Measured by CT, Bone Scans, and Clinical Progression |  | After 8 weeks | 
| Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose |  | In 30 days after the last dose, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Retinoic Acid Receptor Expression on Tissue as Measured by Number of Subjects With the Presence of Peripheral Blood Lymphocytes During the First and Fifth Dose |  | At baseline and 5th week | 
| Duration of Response (Progression-free Survival) as Measured by CT, Bone Scans, and Clinical Progression From Initiation of Therapy Until an Increase of ≥ 25% From the Smallest Sum of All Tumor Measurements Obtained During the Best Response |  | At 6 months and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV renal cell cancer, recurrent renal cell cancer