Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer

Weill Cornell Medicine (WCM)

Status and phase: Completed; Phase 2

Conditions: Kidney Cancer

Treatments: Biological: recombinant interferon alfa; Drug: tretinoin liposome

Study type: Interventional

Funder types: Other

Identifiers

NCT00003656

NYWCCC-0498-209

NCI-V98-1490

9804003327

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

All subjects

Experimental group

Description:

Weekly ATRA-IV with recombinant interferon alfa

Treatment:

Biological: recombinant interferon alfa

Drug: tretinoin liposome