Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over Pharmaceutical / Industry MSKCC-97002 ROCHE-BO15469, NCI-G97-1236

Objectives

I.  Determine the objective response rate for recombinant human interleukin-12 
(IL-12) administered subcutaneously once a week in patients with advanced 
metastatic renal cell carcinoma (RCC), compared to that of interferon alfa-2a 
(Roferon-A).

II.  Evaluate the safety profile of IL-12.

III.  Evaluate the time to response, duration of response, time to 
progression, and survival in patients with RCC.

IV.  Evaluate the pharmacokinetics and pharmacodynamics of IL-12.

V.  Evaluate the potential immunogenicity of IL-12.

VI.  Determine the quality of life of patients with RCC.

Entry Criteria

Disease Characteristics:

Histologically confirmed locally advanced and/or metastatic renal cell
 carcinoma (RCC)

Bidimensionally measurable lesions in at least one site that has not been  
 irradiated (bone lesions, ascites and pleural effusions are not considered as
 measurable)

Minimum indicator lesion size as follows:
 Liver, soft tissue or other masses (evaluable only radiographically) at
  least 20 mm in at least one diameter
 Lung (chest x-ray or CT scan) at least 10 mm in at least one diameter
 Skin lesions and lymph nodes measurable clinically at least 10 mm in at
  least one diameter

No known clinical or CT evidence of CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:
 No prior immunotherapy for RCC, including biologic response modifiers,
  cytokines, monoclonal antibodies or antitumor vaccines

Chemotherapy:
 No prior chemotherapy for RCC

Endocrine therapy:
 No prior hormone therapy for RCC
 No corticosteroids in the last 6 weeks or other systemic corticosteroids at
   treatment start

Radiotherapy:
 Not specified

Surgery:
 Not specified

Patient Characteristics:

Age:
 18 and over
 
Performance status:
 Karnofsky 80%-100%

Hematopoietic:
 WBC at least 3,000/mm3
 Granulocyte count at least 2,000/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 9 g/dL (may be transfused prior to study entry)
 PT or PTT no greater than upper limit of normal (ULN)
 
Hepatic:
 Serum bilirubin no greater than 1.5 times ULN, except for patients with
  Gilbert's syndrome
 SGPT and/or SGOT no greater than 2.5 times ULN (no greater than 4.0 times
  ULN if patient has liver metastasis)
 Alkaline phosphatase no greater than 2.5 times ULN (no greater than 4.0
  times ULN if patient has liver metastasis)
 No prior history of liver disease

Renal:
 Serum creatinine no greater than 1.5 times ULN


Cardiovascular:
 No clinically significant cardiac or cardiovascular abnormalities

Pulmonary:
 No chronic obstructive pulmonary disease

Other:
 Not pregnant or nursing
 Effective contraception required for fertile men or women
 No prior or concurrent malignancy, except basal cell carcinoma of the skin
  and/or carcinoma in situ of the cervix, within the last 5 years
 Negative for HIV, hepatitis B virus, and hepatitis C virus
 No major organ grafts
 No ulcerative colitis or Crohn's disease
 No active infections
 No autoimmune diseases
 No significant bleeding disorders
 No history of psychiatric disorders, seizures or other significant CNS
  disorders
 No other serious medical conditions

Expected Enrollment

150 patients will be accrued.

Outline

This is an open label, multicenter, multinational, randomized, parallel group 
study.  

Patients are randomized to either IL-12 (Group A) or interferon alfa-2a (Group 
B) in a ratio of 2:1.  Patients in Group A receive IL-12 subcutaneously once 
weekly for 3 weeks followed by 1 week of rest, for a total duration of 24 
weeks.  Patients in Group B receive interferon alfa-2a subcutaneously three 
times weekly for a total duration of 24 weeks.  

Patients with no evidence of progressive disease at the end of 24 weeks may be 
continued on therapy until disease progression at the discretion of the 
investigator and Hoffmann-La Roche.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Robert Motzer, MD, Protocol chair		Ph: 646-422-4312; 800-525-2225