Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis

The PERCY Quattro trial has been designed to evaluate the survival benefit of two cytokine treatments, Interleukin-2 (IL2) and/or alpha interferon (IFN), for patients with intermediate chance of response in metastatic renal cell carcinoma.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2.

The primary objective of the study is overall survival; secondary objectives are progression-free survival, response rate, toxicity, and quality of life.

The PERCY Quattro trial has been designed to evaluate the survival benefit of Interleukin-2 (IL2) and/or alpha interferon (IFN) for patients with intermediate chance of response in metastatic renal cell carcinoma.

The primary objective is overall survival, and secondary objectives are progression-free survival, response rate, toxicity, and quality of life assessed before and after induction treatment (week 10).

Patients above 18 years of age are eligible if they have histologically confirmed, clearly progressive metastatic renal carcinoma, more than one metastatic organ and good performance status (Karnofsky score ≥80%), or one metastatic organ with Karnofsky score 80%, normal blood and liver functions with creatinine level \<= 160 µmol/L.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2. The planned sample size is 456 patients (114 in each of the four arms). MPA is given orally as 200 mg daily. IFN is given subcutaneously as 9 million IU three times a week. IL2 is given subcutaneously on a four-week schedule: 9 million IU twice daily for five days followed by a two-day rest, then, on the following three weeks, 9 million IU twice daily for two days then 9 million IU once daily on the following three days; after a week of rest, an identical 4-week cycle is administered. IFN and IL2 combination is given using identical routes, schedules and doses except for a reduction of IFN dose to 6 million IU per injection.

Eligibility Criteria:
Inclusion Criteria:

* Progressive histologically proven metastatic renal cell carcinoma.
* Patient with only 1 metastatic site and Karnofsky = 80% or more than 1 metastatic site and Karnofsky \>= 80%.
* Age \>= 18
* No wide-field radiation therapy for 6 weeks at least.
* No active brain metastasis.
* Blood values within limits of normal (hematocrit \> 30% and leukocyte count \>= 4x109/l and platelet count \>= 120x109/l).
* Creatinine \< 150 µmol/l and bilirubin \<= normal.
* Female patients of childbearing potential: effective method of contraception is necessary.
* Written, voluntary, informed consent.

Exclusion Criteria:

* Previous treatment with cytokines.
* Only one metastatic organ and Karnofsky = 90% or 100% (inclusion in good prognosis group).
* More than one metastatic organ (at least one metastasis to the liver) and \<12 months between initial diagnosis and diagnosis of metastasis.
* Active brain metastases.
* Patient with concurrent grade III/IV heart disorder (congestive heart failure, coronary artery disease, uncontrolled hypertension, severe arrhythmia, etc) and/or stroke volume \< 50%.
* Severe pulmonary, hepatic, or renal disease potentially aggravated by treatment.
* Severe concurrent infection necessitating antibiotics
* Patient with known HIV or AIDS-related disease, or presence of HB antigen or known chronic hepatitis.
* Previous allograft.
* Patient under corticosteroid treatment.
* Previous or concurrent primary malignancies at other sites (except from baso-cellular skin cancer or cervical cancer in situ)
* Pregnant or lactating woman.
* Follow-up difficult because of geography or personal circumstances.