Clinical trial NCT00142415
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Advanced Renal Cell Carcinoma Clear Cell Renal Cell Carcinoma (CCRCC) Lutetium-177 177-Lu cG250 DOTA-cG250 Monoclonal Antibody
Sponsor: Ludwig Institute for Cancer Research
Start date: 2005-02-01; Completion date: 2011-01-01
Enrollment: 26 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This was a Phase I/II, single-center, dose-escalation study. 177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250 (177-Lu-DOTA-cG250) was administered at a starting dose of 30 mCi/m\^2 of 177-Lu (fixed dose of 10 mg cG250) and escalated in increments of 10 mCi/m\^2 of 177-Lu in sequentially enrolled cohorts according to a standard 3 + 3 design until determination of the maximum tolerated dose (MTD). The primary objectives were to determine the safety, targeting, and dosimetry of 177-Lu-DOTA-cG250 in subjects with advanced renal cell carcinoma. The secondary objective was measurement of tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Detailed description:
Prior to administration of 177-Lu-DOTA-cG250, subjects received 5 mCi/10 mg of the 111-Indium-DOTA-cG250 (111-In-DOTA-cG250) antibody (an imaging dose). Whole body and blood measurements of radioactivity were obtained on at least 3 occasions for 1 week to determine targeting and dosimetry. If at least one known and evaluable metastatic lesion was visualized with 111-In-DOTA-cG250, a single dose of therapeutic 177-Lu-DOTA-cG250 was administered the following week. In the absence of disease progression and after recovery from toxicity, subjects may have been retreated no sooner than 12 weeks after the previous treatment with a dose of no more than 75% of the previous dose, for a total of not more than 3 treatments. Only subjects with normal pharmacokinetics on the diagnostic 111-In-DOTA-cG250 study (indicative of human anti-chimeric antibody \[HACA\] negativity) were eligible for re-treatment.

Subjects in the initial cohort were enrolled sequentially to receive 30 mCi/m\^2 of 177-Lu-DOTA-cG250 (fixed dose of 10 mg cG250). In the absence of a dose-limiting toxicity, the dose was escalated in each subsequent cohort in 10 mCi/m\^2 increments of 177-Lu. At least 3 subjects per dose level were followed for up to 12 weeks with imaging, biochemical, and hematologic tests. Safety was monitored continuously throughout the study.

Arms: arm 1: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m\^2 of 177-Lu. arm 2: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m\^2 of 177-Lu. arm 3: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m\^2 of 177-Lu. arm 4: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m\^2 of 177-Lu. arm 5: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m\^2 of 177-Lu. arm 6: Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m\^2 of 177-Lu.
Interventions: intervention 1: 111-In-DOTA-cG250 intervention 2: 177-Lu-DOTA-cG250
Intervention descriptions: intervention 1: On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In. intervention 2: On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m\^2 in the initial cohort.

Protocol documents: