Combined Treatment With Capecitabine and Immunotherapy Versus Immunotherapy Alone in Advanced Renal Cell Carcinoma

Multi-center, prospective randomised phase III study evaluating capecitabine in combination with standard-immunotherapy versus standard-immunotherapy alone as first-line therapy in patients with metastatic renal cell carcinoma.

Treatment plan Group A

Patients randomised to group A will receive treatment according to the following treatment schedule:

Group A: Combined Chemo-Immunotherapy Chemotherapy: Mo-Fr Immunotherapy

* Week 1:Capecitabine / Interferon;
* Week 2:Capecitabine / Interferon;
* Week 3:REST PERIOD / Interleukin;
* Week 4:Capecitabine / Interleukin;
* Week 5:Capecitabine / REST PERIOD;
* Week 6:REST PERIOD / Interferon;
* Week 7:Capecitabine / Interferon;
* Week 8:Capecitabine / Interleukin;
* Week 9:REST PERIOD / Interleukin;
* Week 10:Capecitabine / REST PERIOD;
* Week 11:Capecitabine / Interferon;
* Week 12:REST PERIOD / Interferon;
* Week 13:Capecitabine / Interleukin;
* Week 14:Capecitabine / Interleukin;

DOSAGES AND ROUTES OF ADMINISTRATION:

Capecitabine orally from day 1 to 14 at a dose of 1000 mg/m2 twice daily every 21 days.

Interferon-alpha subcutaneously on days 1 + 3 + 5 weeks 1 + 2 +6 + 7,11+12 at a dose of 6 MIU/d.

Interleukin-2 subcutaneously on days 1 to 4 in weeks 3 + 4 +8 + 9,13+14 at a dose of 4.5 MIU/day.

Group B

Patients randomized to group B will receive treatment according to the same treatment schedule and at the same dosages without capecitabine.

Efficacy evaluations will be performed every 14 weeks of treatment in both groups

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed renal cell carcinoma (primary tumour or biopsy/surgery of metastases)
* Radiologically confirmed metastatic disease
* Surgically removed primary tumour so feasible (nephrectomy or nephron-sparing surgery as indicated)
* Karnofsky-Performance Status \>70%
* Age 19-75 years
* Life expectancy of at least 3 months
* Adequate bone marrow function (i.e. white blood cell count above 3000/μL, platelet count above 75 000 /μL, hemoglobin above 9 mg/dl)
* Adequate organ function (i.e. serum creatinine, bilirubin and AST below 1.25 x the upper limit of the institutions' normal range)
* Negative pregnancy test for female patients
* Written informed consent

Exclusion Criteria:

* Age \<19 or \>75 years
* Karnofsky-Performance Status \< 70%
* Untreated or uncontrolled brain metastases
* Second neoplasia
* Primary tumour surgically removable
* Solitary, surgically removable metastases
* Major concomitant diseases of the cardiovascular, respiratory or renal systems, as well as active systemic infections
* Severe renal disease or liver insufficiency or myeloid dysfunction (including patients with a history of a disease that is likely to interfere with the metabolism or excretion of the test medication)
* Other less common diseases as peptic ulcer disease, inflammatory bowel disease, autoimmune disease (severe known psoriasis, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
* Drug addiction (including excessive alcohol consumption) within 1 year prior to study start.
* History of other conditions consistent with decompensated liver disease or other evidence of bleeding form esophageal varices.
* History of chronic hepatitis and immunsupressiva
* Known HIV Infection
* Evidence of allergy or hypersensitivity against recombinant Interferon alfa-2a or other components of preparation.
* History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.
* Seizure disorders and /or compromised central nervous system function.
* History of evidence of severe retinopathy
* Patient unwilling or unable to give informed consent
* Pregnancy or breastfeeding