Monoclonal Antibody Therapy in Treating Patients With Advanced Kidney Cancer

Kidney Cancer Clinical Trial

Official title:

Phase I/II Study of 131I-Labeled Chimeric Antibody G250 (131I-cG250) in Patients With Advanced Renal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003102
• Other study ID #: CDR0000065834
• Secondary ID: MSKCC-97049NCI-H
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 17, 1998
• Est. completion date: May 27, 2003

Study information

• Verified date: October 2023
• Source: Ludwig Institute for Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 27, 2003
• Est. primary completion date: April 19, 2000
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria Histologically proven renal cell carcinoma. Clinical presentation consistent with metastatic renal cell carcinoma. Bidimensionally measurable disease by conventional imaging. Patients must have been off chemotherapy or immunotherapy for at least 6 weeks prior to study entry. Women of child-bearing age must have had a negative pregnancy test carried out the day of and prior to receiving therapy, and were asked to use effective contraception during the study. Patients were required to be ambulatory with a Karnofsky Performance Status at least 70, Serum creatinine = 2mg/dl, Serum bilirubin = 1mg/d, White Blood Cells (WBC) = 3,500/mm^3, Platelet count = 100,000/mm^3, Prothrombin time < 1.3 x control. Exclusion Criteria Significant prior radiation therapy to the entire pelvis and/or lumbosacral spine. Clinically significant cardiac disease. Serious infection requiring treatment with antibiotics, or other serious illness. Women who are pregnant or lactating. Central Nervous System (CNS) tumor involvement. Life expectancy less than 6 weeks. Hypercalcemia greater than 12.5 mg/dL or symptomatic.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Biological:
• Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)
cG250 is an IgG1 chimeric monoclonal antibody. It was supplied as a sterile solution at a concentration of 1.0 mg/mL in either a 2 mL or a 5 mL vial. cG250 was radiolabeled with Iodine-131 prior to use.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig Institute for Cancer Research	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Adverse Events (AEs)	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.	Up to 12 months
Primary	Number of Patients With Dose-Limiting Toxicities (DLTs)	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.	up to 12 months
Secondary	Number of Patients With Best Overall Tumor Response	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.	Up to 12 weeks
Secondary	Number of Patients With Human Anti-chimeric Antibodies (HACA)	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.	Up to 6 months