Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Kidney Cancer or Malignant Melanoma

This study has been completed.
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004244
First received: January 28, 2000
Last updated: March 19, 2013
Last verified: June 2005
  Purpose

This phase I trial is studying the side effects and best dose of interleukin-12 and interferon alfa in treating patients with metastatic kidney cancer or malignant melanoma. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of cancer cells. Combining interleukin-12 and interferon alfa may kill more cancer cells.


Condition Intervention Phase
Kidney Cancer
Melanoma (Skin)
Biological: recombinant interferon alfa
Biological: recombinant interleukin-12
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma

Resource links provided by NLM:


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

Enrollment: 30
Study Start Date: March 2000
Study Completion Date: September 2008
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive interleukin-12 SC twice a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

Biological: recombinant interferon alfa Biological: recombinant interleukin-12
Experimental: Arm II

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive interferon alfa SC three times a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

Biological: recombinant interferon alfa Biological: recombinant interleukin-12
Experimental: Arm III

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive treatment with interleukin-12 in combination with interferon alfa at the MTD as described above.

Biological: recombinant interferon alfa Biological: recombinant interleukin-12

Detailed Description:

OBJECTIVES:

I. Determine the toxicity of interleukin-12 and interferon alfa in patients with metastatic renal cell carcinoma or malignant melanoma.

II. Determine the maximum tolerated dose of these drugs when concurrently administered in this patient population.

III. Obtain preliminary data on the antitumor efficacy of this combination in these patients.

OUTLINE: This is a dose-escalation study, followed by a randomized study.

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Once the MTD is established, additional patients are accrued and randomized to 1 of the following treatment arms:

ARM I: Patients receive interleukin-12 SC twice a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

ARM II: Patients receive interferon alfa SC three times a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

ARM III: Patients receive treatment with interleukin-12 in combination with interferon alfa at the MTD as described above.

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for the dose escalation portion of this study. An additional 18 patients (5 in arm I, 5 in arm II, and 8 in arm III) will be accrued to the randomized 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 or cytologically confirmed renal cell carcinoma or malignant melanoma
  • Strong clinical evidence or biopsy proof of metastases to a site or sites distant from the primary tumor
  • Bidimensionally measurable of evaluable disease
  • No significant effusions and/or ascites
  • No more than 3 prior regimens for metastatic disease
  • No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • At least 3 months

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.5 g/dL

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • ALT/AST no greater than 3 times upper limit of normal

Renal:

  • Creatinine no greater than 1.8 mg/dL
  • Calcium no greater than 11.5 mg/dL

Cardiovascular:

  • No history of serious cardiac arrhythmia or cardiac arrhythmia requiring treatment
  • No congestive heart failure
  • No angina pectoris
  • No New York Heart Association class III or IV heart disease

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active peptic ulcer
  • No autoimmune disease
  • No inflammatory bowel disease
  • No local or systemic infections requiring IV antibiotics within the past 28 days
  • No known seizure disorder
  • No other prior malignancy except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any curatively treated malignancy in complete remission for at least 3 years
  • HIV, hepatitis B surface antigen, and hepatitis C negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Recovered from prior biologic therapy

Chemotherapy:

  • Recovered from prior chemotherapy

Endocrine therapy:

  • At least 28 days since prior hormonal therapy and recovered
  • No concurrent corticosteroids except for replacement steroids

Radiotherapy:

  • Recovered from prior radiotherapy
  • At least 28 days since prior radiotherapy for control of pain from skeletal lesions

Surgery:

  • At least 28 days since prior major surgery requiring general anesthesia
  • No organ allografts

Other:

  • No concurrent aspirin
  • No concurrent barbiturates
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004244

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Study Chair: Ronald M. Bukowski, MD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004244     History of Changes
Other Study ID Numbers: CDR0000067489, CCF-IRB-3063, NCI-T99-0028
Study First Received: January 28, 2000
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage IV renal cell cancer
recurrent renal cell cancer
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Melanoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interferon-alpha
Interferon Alfa-2a
Interferons
Interleukin-12
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on April 14, 2014