Monoclonal Antibody Therapy in Treating Patients With Advanced Kidney Cancer

Phase 1

Completed

Conditions: Kidney Cancer

Interventions: Biological: Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)

Registration Number: NCT00003102

Lead Sponsor: Ludwig Institute for Cancer Research

Brief Summary: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients with advanced kidney cancer.

Detailed Description: This is a dose-escalation study. Initially patients receive a scout dose of iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250) administered intravenously (IV) over 10 minutes to determine whole body clearance. One week later, patients receive incremental doses of 131I-cG250 IV over 10 minutes at 2-3 day intervals for 2-6 weeks,. Dose escalation begins at least 8 weeks after the last infusion of 131I-cG250. In the absence of dose-limiting toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of 131I-cG250 on the same schedule. If dose-limiting toxicity occurs in 2 of 6 patients treated at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose (MTD). Treatment continues once recovery from all toxic effects occurs, beginning 8 to 12 weeks following the last dose of 131I-cG250. Patients achieving complete remission, partial remission, or stable disease were eligible to receive up to 3 courses of treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1 50cGy radiation	Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)	On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes. Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131. In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.
Cohort 2 75cGy radiation	Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)	On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes. Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131. In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.
Cohort 3 100cGy radiation	Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)	On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes. Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131. In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Adverse Events (AEs)	Up to 12 months	All adverse events occurring during the study were to be recorded on the patient's case report form, and include the following information: a description; date of onset and resolution; severity; relationship to an investigational agent; action taken and outcome. Toxicity was graded in accordance with the NCI CTCAE version 3.0.
Number of Patients With Dose-Limiting Toxicities (DLTs)	up to 12 months	Subjects were monitored for Adverse Events (AEs) for at least 8 weeks after the last infusion of 131I-cG250, or until recovery from all toxicity, and prior to dose escalation. Toxicity was graded in accordance with the Common Toxicity Criteria (CTC) of the National Cancer Institute (NCI) Version 3.0. Dose-Limiting Toxicity (DLT) was defined as grade 3 or greater toxicity related to study therapy. The maximum tolerated dose was defined as the highest safely tolerated dose where at most one of six patients experiences a DLT with the next higher dose having at least two patients who experience a DLT.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Best Overall Tumor Response	Up to 12 weeks	Tumor responses were evaluated using computed tomography and categorized according to World Health Organization (WHO) criteria at baseline and at no more than 6 weeks after the last dose, or not more than 12 weeks after entry into the study. Complete Response (CR): disappearance of all measurable disease lasting at least 1 month; Partial Response (PR): ≥ 50% decrease in the size of the product of 2 perpendicular diameters of any measurable lesions and no new lesions, lasting at least one month; Progressive Disease (PD): ≥ 25% increase in the size of any measurable lesions or the appearance of any new lesions; Stable Disease (SD): small changes that do not meet above criteria.
Number of Patients With Human Anti-chimeric Antibodies (HACA)	Up to 6 months	Blood samples were taken at baseline and in weeks 2, 3, 4, 5, and 6 as well as month 6. HACA was measured by an enzyme-linked immunosorbent assay (ELISA) using the "double antibody sandwich" technique and pretreatment serum as negative control.