Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma
18 Years
N/A
Both
Kidney Cancer, Melanoma (Skin)
Trial Information
Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Ronald M. Bukowski, MD
Investigator Role:
Study Chair
Investigator Affiliation:
The Cleveland Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000067489
NCT ID:
NCT00004244
Start Date:
March 2000
Completion Date:
September 2008
Related Keywords:
- Kidney Cancer
- Melanoma (Skin)
- stage IV renal cell cancer
- recurrent renal cell cancer
- stage IV melanoma
- recurrent melanoma
- Carcinoma, Renal Cell
- Kidney Neoplasms
- Melanoma
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
