Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer - Full Text View

Sponsor:	Weill Medical College of Cornell University
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003656

Purpose

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.

Condition	Intervention	Phase
Kidney Cancer	Biological: recombinant interferon alfa Drug: tretinoin liposome	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Trial of Atragen and Interferon Alfa-2b in Patients With Advanced Renal Cell Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer

Drug Information available for: Interferon alfa-2a Interferon alfa-n1 Tretinoin Interferons

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response as measured by CT, bone scans, and clinical progression at 8 weeks after first dose [ Designated as safety issue: No ]
Toxicity by clinical evaluation from first dose to 30 days after last dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Retinoic acid receptor expression on tissue as measured by the presence of peripheral blood lymphocytes during the first and fifth dose [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]

Estimated Enrollment:	43
Study Start Date:	January 1999

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003656

Locations

United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Study Chair:

David M. Nanus, MD

Weill Medical College of Cornell University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Study ID Numbers:	CDR0000066748, NYWCCC-0498-209, NCI-V98-1490
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003656 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV renal cell cancer
recurrent renal cell cancer

Additional relevant MeSH terms:

Anti-Infective Agents
Interferon Type I, Recombinant
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Urogenital Neoplasms
Urologic Neoplasms
Keratolytic Agents
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Therapeutic Uses
Growth Inhibitors
Kidney Diseases
Angiogenesis Modulating Agents

Dermatologic Agents
Interferon-alpha
Neoplasms by Histologic Type
Growth Substances
Interferons
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Carcinoma, Renal Cell
Tretinoin
Adenocarcinoma
Interferon Alfa-2a
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009