• To determine the safety of increasing doses of 177Lu-DOTA-cG250 in patients with advanced renal cancer to establish the MTD [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• To determine the targeting and dosimetry of 177Lu-DOTA-cG250 in patients with advanced renal cancer, using 111In-DOTA-cG250 as a surrogate. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

• 1)To determine the safety of increasing doses of 177Lu-DOTA-cG250 in patients with advanced renal cancer to establish the MTD
• 2)To determine the targeting and dosimetry of 177Lu-DOTA-cG250 in patients with advanced renal cancer, using 111In-DOTA-cG250 as a surrogate.

The purpose of this study is to determine whether 177Lu-DOTA-cG250 is effective for treatment of patients with advanced renal cell carcinoma

This is a Phase I/II dose escalation study using 177Lu-DOTA-cG250 for treatment of patients with advanced renal cell carcinoma. The trial requires a minimum of 6 patients and a maximum of 18 patients. The initial group of patients will be treated with 30 mCi/m2 of Lu-177. Subsequent treatments will be in 10 mCi/m2 increments. At least three patients per dose level will be followed for up to 12 weeks with imaging, biochemical and hematologic tests to determine the safety of 177Lu-DOTA-cG250. CT scans will be carried out at baseline and after 12 weeks (or after recovery from toxicity), for response assessment. Patients will initially receive 5 mCi/10 mg 111In-DOTA-cG250 antibody (an imaging dose preceeding Lu-177-cG250 treatment). Whole body and blood measurements of radioactivity will be obtained on at least three occasions for one week to determine targeting and dosimetry. Only if at least one known and evaluable metastatic lesion is visualized with In-111-cG250, therapeutic 177Lu-DOTA-cG250 will be administered the following week. In the absence of disease progression and after recovery from toxicity, patients may be retreated no sooner than 12 weeks after the prior treatment with a dose of no more than 75% of the previous dose, for a total of not more than three treatments. Only patients who have normal pharmacokinetics on the preceding diagnostic In-111-cG250 study (indicative of HACA negativity) are eligible for retreatment.

• Drug: cG250-In111
• Drug: cG250-Lu177

Inclusion Criteria:

1. Patients with proven advanced and progressive renal cell carcinoma of the clear cell type
2. At least one evaluable lesion less than 5 cm
3. Performance status: Karnofsky > 70 %

4. Laboratory values obtained less than 14 days prior to registration:• White blood cells (WBC) > 3.5 x 109/l

   • Platelet count > 100 x 109/l
   • Hemoglobin > 6 mmol/l
   • Total bilirubin < 2 x upper limit of normal (ULN)
   • ASAT, ALAT < 3 x ULN (< 5 x ULN if liver metastases present)
   • Serum creatinine < 2 x ULN
5. Negative pregnancy test for women of childbearing potential (urine or serum)
6. Age over 18 years
7. Ability to provide written informed consent

Exclusion Criteria:

1. Known metastases to the brain
2. Untreated hypercalcemia
3. Metastatic disease limited to the bone
4. Pre-exposure to murine/chimeric antibody therapy
5. Chemotherapy, external beam radiation or immunotherapy within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed, when unirradiated, evaluable lesions elsewhere are present.
6. Cardiac disease with New York Heart Association classification of III or IV
7. Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception
8. Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgement of the investigator will significantly affect patients' clinical status
9. Life expectancy shorter than 6 months.