Treatment of Patients With Advanced Renal Cancer With a Radiolabeled Antibody, Yttrium-90 Conjugated Chimeric G250

Patients were enrolled sequentially into cohorts of 3 to 6 patients until determination of the maximum tolerated dose (MTD) of ^90Y-DOTA-cG250, defined as the dose level below the dose at which ≥ 2 patients experienced dose-limiting toxicity (DLT). In an attempt to mitigate liver uptake and toxicity, patients initially received a nontherapeutic injection with ^111In-DOTA-cG250 at an imaging dose of 5 mCi of ^111In + 10 mg of cG250 on Day 1. Whole body and blood measurements of radioactivity were obtained on at least 3 occasions for 1 week to determine targeting and dosimetry. Provided that protocol-specified criteria were met, including targeting to lesions > 2 cm detected on computed tomography (CT) scan, a single dose of therapeutic ^90Y-DOTA-cG250 was administered on Day 8, 9, or 10. The starting dose of ^90Y-DOTA-cG250 was 0.2 mCi/kg of ^90Y + 10 mg of cG250 administered as an intravenous (IV) infusion, with escalation of the ^90Y dose in subsequent cohorts in 0.05 to 0.1 mCi/kg increments.

Patients were treated in an outpatient setting and were observed for at least 2 hours following each infusion, at which point vital signs and blood samples were obtained. Patients were followed for 6 to 8 weeks post-treatment (or after recovery from toxicity) with imaging, biochemical, serological, and hematologic tests to determine the safety of ^90Y-DOTA-cG250 and to inform dose-escalation decisions. Extent of disease evaluations, preferably by positron emission tomography (PET)/CT or standard CT, were performed at baseline and 6 to 8 weeks post-treatment (or after recovery from toxicity). Long-term follow-up was performed, when possible, every 12 weeks thereafter for up to 2 years.

Inclusion criteria

• All patients must have had histologically proven clear cell renal carcinoma.
• Age ≥ 18 years. Children were not enrolled because clear cell renal cancer is rarely seen in children.
• All patients must have had a clinical presentation consistent with metastatic renal carcinoma.
• Patients must have had bidimensionally measurable disease by conventional imaging methods including radiography, ultrasound, CT, or other anatomic imaging modalities. Lesions seen on skeletal scintigraphy alone were not considered measurable.
• Female patients of childbearing age were required to have a negative pregnancy test carried out the day of and prior to receiving therapy, and were asked to use effective contraception during the study.
• All patients must have been ambulatory with a Karnofsky Performance Status of at least 70.
• The following laboratory results within the last 2 weeks prior to study Day 1:

• serum creatinine ≤ 2.0 mg/dL
• serum bilirubin (total) ≤ 2.0 mg/dL
• aspartate aminotransferase (AST) ≤ 2.5 × the upper limit of normal (ULN)
• alanine aminotransferase (ALT) ≤ 2.5 × ULN
• white blood cell (WBC) count ≥ 3500/mm^3
• platelet count ≥ 100,000/mm^3
• prothrombin time ≤ 1.3 × control
• Able and willing to give valid written informed consent.

Exclusion criteria

• Significant prior radiotherapy (> 30 Gy) to the entire pelvis and/or lumbosacral spine.
• Clinically significant cardiac disease (New York Heart Association Class [III/IV]).
• Serious infection requiring treatment with antibiotics, or other serious illness.
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to study agent administration.
• Survival expectancy of less than 12 weeks.
• Patients with central nervous system (CNS) involvement were excluded under the following criteria:

• Brain metastasis, except for stable disease over 3 months.
• Untreated brain metastasis.
• Evidence of progression of neurologic CNS involvement within 3 months prior to entering the protocol.
• Hypercalcemia > 12.5 mg/100 mL or symptomatic.
• Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
• Lack of availability of the patient for clinical and laboratory follow-up assessment.
• Patients known to have hepatobiliary disease and/or human immunodeficiency virus/acquired immune deficiency syndrome.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
• Pregnancy or breastfeeding.
• Refusal or inability to use effective means of contraception in men or women of childbearing potential.