Treatment of Patients With Advanced Renal Cancer With a Radiolabeled Antibody, Yttrium-90 Conjugated Chimeric G250
Condition: Renal Cell Carcinoma; Kidney Neoplasm; Renal Cancer; Kidney Cancer
MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250)
Intervention description: Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Patients were enrolled sequentially in cohorts of 3 to 6 patients to receive escalating doses of study treatment until determination of the MTD.
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: antibody; renal cell carcinoma; advanced renal cancer; cG250; ^90Y

Summary:

      This was a Phase 1, open-label, dose-escalation study of yttrium-90 conjugated chimeric G250
      (^90Y-DOTA-cG250) in patients with advanced, measurable clear cell renal cell carcinoma
      (RCC). Study objectives were to determine the safety, targeting, and dosimetry of
      ^90Y-DOTA-cG250, using indium-111 conjugated chimeric G250 (^111In-DOTA-cG250) as a
      surrogate, as well as to evaluate the immunogenicity of cG250.
    

Eligibility criteria:

        Inclusion Criteria:

          1. All patients must have had histologically proven clear cell renal carcinoma.

          2. Age ≥ 18 years. Children were not enrolled because clear cell renal cancer is rarely
             seen in children.

          3. All patients must have had a clinical presentation consistent with metastatic renal
             carcinoma.

          4. 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.

          5. 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.

          6. All patients must have been ambulatory with a Karnofsky Performance Status of at least
             70.

          7. 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

          8. Able and willing to give valid written informed consent.

        Exclusion Criteria:

          1. Significant prior radiotherapy (> 30 Gy) to the entire pelvis and/or lumbosacral
             spine.

          2. Clinically significant cardiac disease (New York Heart Association Class [III/IV]).

          3. Serious infection requiring treatment with antibiotics, or other serious illness.

          4. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to study agent
             administration.

          5. Survival expectancy of less than 12 weeks.

          6. 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.

          7. Hypercalcemia > 12.5 mg/100 mL or symptomatic.

          8. Mental impairment that may have compromised the ability to give informed consent and
             comply with the requirements of the study.

          9. Lack of availability of the patient for clinical and laboratory follow-up assessment.

         10. Patients known to have hepatobiliary disease and/or human immunodeficiency
             virus/acquired immune deficiency syndrome.

         11. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to enrollment.

         12. Pregnancy or breastfeeding.

         13. Refusal or inability to use effective means of contraception in men or women of
             childbearing potential.