Clinical trial NCT00003656: Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer
Official title: Phase II Trial of Atragen and Interferon Alfa-2b in Patients With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: stage IV renal cell cancer
recurrent renal cell cancer
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Best Response as Measured by CT, Bone Scans, and Clinical Progression
timeFrame: After 8 weeks
measure: Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose
timeFrame: In 30 days after the last dose, an average of 1 year.
Secondary outcomes:
measure: 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
timeFrame: At baseline and 5th week
measure: 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
timeFrame: At 6 months and 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: David M. Nanus, MD
role: STUDY_CHAIR
References:
citation: Goldberg JS, Vargas M, Rosmarin AS, Milowsky MI, Papanicoloau N, Gudas LJ, Shelton G, Feit K, Petrylak D, Nanus DM. Phase I trial of interferon alpha2b and liposome-encapsulated all-trans retinoic acid in the treatment of patients with advanced renal cell carcinoma. Cancer. 2002 Sep 15;95(6):1220-7. doi: 10.1002/cncr.10809.