Clinical trial NCT00199875
Conditions: Renal Cell Carcinoma Kidney Neoplasm Renal Cancer Kidney Cancer
Keywords: antibody renal cell carcinoma advanced renal cancer cG250 ^90Y
Sponsor: Ludwig Institute for Cancer Research
Start date: 2005-07-06; Completion date: 2013-03-14
Enrollment: 18 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief 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.

Detailed description:
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.

Arms: arm 1: Patients initially received a nontherapeutic injection of \^111In-DOTA-cG250 (5 mCi \^111In + 10 mg cG250) on Day 1. Pending satisfaction of protocol-specified lesion targeting criteria, a single dose of therapeutic \^90Y-DOTA-cG250 (0.2 mCi/kg \^90Y + 10 mg cG250) was administered on Day 8, 9, or 10 as a continuous IV infusion over approximately 5 to 15 minutes. arm 2: Patients initially received a nontherapeutic injection of \^111In-DOTA-cG250 (5 mCi \^111In + 10 mg cG250) on Day 1. Pending satisfaction of protocol-specified lesion targeting criteria, a single dose of therapeutic \^90Y-DOTA-cG250 (0.3 mCi/kg \^90Y + 10 mg cG250) was administered on Day 8, 9, or 10 as a continuous IV infusion over approximately 5 to 15 minutes. arm 3: Patients initially received a nontherapeutic injection of \^111In-DOTA-cG250 (5 mCi \^111In + 10 mg cG250) on Day 1. Pending satisfaction of protocol-specified lesion targeting criteria, a single dose of therapeutic \^90Y-DOTA-cG250 (0.4 mCi/kg \^90Y + 10 mg cG250) was administered on Day 8, 9, or 10 as a continuous IV infusion over approximately 5 to 15 minutes. arm 4: Patients initially received a nontherapeutic injection of \^111In-DOTA-cG250 (5 mCi \^111In + 10 mg cG250) on Day 1. Pending satisfaction of protocol-specified lesion targeting criteria, a single dose of therapeutic \^90Y-DOTA-cG250 (0.45 mCi/kg \^90Y + 10 mg cG250) was administered on Day 8, 9, or 10 as a continuous IV infusion over approximately 5 to 15 minutes. arm 5: Patients initially received a nontherapeutic injection of \^111In-DOTA-cG250 (5 mCi \^111In + 10 mg cG250) on Day 1. Pending satisfaction of protocol-specified lesion targeting criteria, a single dose of therapeutic \^90Y-DOTA-cG250 (0.55 mCi/kg \^90Y + 10 mg cG250) was administered on Day 8, 9, or 10 as a continuous IV infusion over approximately 5 to 15 minutes.
Interventions: intervention 1: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250)
Intervention descriptions: intervention 1: Patients received a single infusion of \^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.

Protocol documents: