Monoclonal Antibody Therapy in Treating Patients With Advanced Kidney Cancer

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003102
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 15
• Location: 1
• Arms: 3
• Actual Duration (Months): 54.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Biological: Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250)	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of 131I-Labeled Chimeric Antibody G250 (131I-cG250) in Patients With Advanced Renal Carcinoma
• Actual Study Start Date: Nov 17, 1998
• Actual Primary Completion Date: Apr 19, 2000
• Actual Study Completion Date: May 27, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 50cGy radiation 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.	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.
Experimental: Cohort 2 75cGy radiation 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.	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.
Experimental: Cohort 3 100cGy radiation 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.	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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• National Cancer Institute (NCI)

Investigators

• Study Chair: Chaitanya R. Divgi, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00003102
• Other Study ID Numbers: CDR0000065834; MSKCC-97049; NCI-H97-0004; LUD 96-006
• First Posted: Aug 12, 2004
• Last Update Posted: Jan 5, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Ludwig Institute for Cancer Research: stage IV renal cell cancer; recurrent renal cell cancer
• Additional relevant MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.	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 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. 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.	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 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. 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.
Period Title: Overall Study
STARTED	3	9	3
COMPLETED	2	6	1
NOT COMPLETED	1	3	2

Baseline Characteristics

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation	Total
Arm/Group Description	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 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. Iiodine-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.	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 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. 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.	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 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. 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.	Total of all reporting groups
Overall Participants	3	9	3	15
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	8 88.9%	2 66.7%	13 86.7%
>=65 years	0 0%	1 11.1%	1 33.3%	2 13.3%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 11.1%	2 66.7%	4 26.7%
Male	2 66.7%	8 88.9%	1 33.3%	11 73.3%
Region of Enrollment (participants) [Number]
United States	3 100%	9 100%	3 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Adverse Events (AEs)
Description	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.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of 131I-cG250.

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.	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 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. 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.	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 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. 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.
Measure Participants	3	9	3
Count of Participants [Participants]	3 100%	8 88.9%	3 100%

2. Primary Outcome

Title	Number of Patients With Dose-Limiting Toxicities (DLTs)
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of 131I-cG250.

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.	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 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. 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.	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 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. 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.
Measure Participants	3	9	3
Count of Participants [Participants]	0 0%	1 11.1%	3 100%

3. Secondary Outcome

Title	Number of Patients With Best Overall Tumor Response
Description	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.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

All patients who received study treatment and had at least one pre- and post-treatment tumor measurement.

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.	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 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. 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.	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 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. 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.
Measure Participants	3	7	2
Complete Response (CR)	0 0%	0 0%	0 0%
Partial Response (PR)	0 0%	0 0%	0 0%
Stable Disease (SD)	2 66.7%	6 66.7%	1 33.3%
Progressive Disease (PD)	1 33.3%	1 11.1%	1 33.3%

4. Secondary Outcome

Title	Number of Patients With Human Anti-chimeric Antibodies (HACA)
Description	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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

All patients who received study therapy and had blood samples taken for HACA analyses before and after treatment.

Arm/Group Title	Cohort 1 50cGy Radiation	Cohort 2 75cGy Radiation	Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.	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 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. 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.	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 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. 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.
Measure Participants	3	9	3
Number of subjects with negative HACA before and after treatment	2 66.7%	8 88.9%	3 100%
Number of subjects with negative HACA before treatment and positive HACA after treatment	1 33.3%	1 11.1%	0 0%

Adverse Events

Time Frame	up to 12 months
Adverse Event Reporting Description	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.
Arm/Group Title	Cohort 1 50cGy Radiation		Cohort 2 75cGy Radiation		Cohort 3 100cGy Radiation
Arm/Group Description	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 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. 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.		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 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. 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.		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 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. 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.
All Cause Mortality
	Cohort 1 50cGy Radiation		Cohort 2 75cGy Radiation		Cohort 3 100cGy Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/9 (0%)		2/3 (66.7%)
Serious Adverse Events
	Cohort 1 50cGy Radiation		Cohort 2 75cGy Radiation		Cohort 3 100cGy Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/9 (22.2%)		3/3 (100%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)		1/9 (11.1%)		2/3 (66.7%)
Thrombocytopenia	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Neutropenia	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Infections and infestations
Urinary tract infection	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Sepsis	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Vascular disorders
Cerebrovascular accident	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Cohort 1 50cGy Radiation		Cohort 2 75cGy Radiation		Cohort 3 100cGy Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		8/9 (88.9%)		3/3 (100%)
Cardiac disorders
Palpitations	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Dypsnea	2/3 (66.7%)		3/9 (33.3%)		1/3 (33.3%)
Oedema peripheral	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		2/9 (22.2%)		2/3 (66.7%)
Abdominal distention	0/3 (0%)		2/9 (22.2%)		0/3 (0%)
Faeces discolored	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Constipation	1/3 (33.3%)		2/9 (22.2%)		0/3 (0%)
Diarrhea	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Dry mouth	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Flatulence	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Gastrointestinal pain	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Hemorrhoids	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Melena	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Nausea	2/3 (66.7%)		5/9 (55.6%)		1/3 (33.3%)
Odynophagia	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Stomatitis	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Taste disorder	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Vomiting	1/3 (33.3%)		1/9 (11.1%)		0/3 (0%)
General disorders
Feeling cold	1/3 (33.3%)		1/9 (11.1%)		0/3 (0%)
Fatigue	2/3 (66.7%)		4/9 (44.4%)		2/3 (66.7%)
Pyrexia	1/3 (33.3%)		1/9 (11.1%)		1/3 (33.3%)
Chills	1/3 (33.3%)		1/9 (11.1%)		0/3 (0%)
Immune system disorders
Hypersensitivity	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Investigations
Breath sounds abnormal	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Weight decreased	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Metabolism and nutrition disorders
Anorexia	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Decreased appetite	0/3 (0%)		2/9 (22.2%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Groin pain	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Flank pain	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Arthralgia	0/3 (0%)		3/9 (33.3%)		0/3 (0%)
Pain in extremity	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Myalgia	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Neck pain	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Nervous system disorders
Dysuria	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Dizziness	1/3 (33.3%)		2/9 (22.2%)		1/3 (33.3%)
Headache	1/3 (33.3%)		2/9 (22.2%)		0/3 (0%)
Insomnia	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Renal and urinary disorders
Costovertebral angle tenderness	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Pollakiuria	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Hematuria	0/3 (0%)		2/9 (22.2%)		0/3 (0%)
Nocturia	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Urinary hemmorhage	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Chest pain	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Cough	0/3 (0%)		2/9 (22.2%)		1/3 (33.3%)
Epistaxis	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Influenza	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Nasal congestion	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Rhinitis	0/3 (0%)		0/9 (0%)		1/3 (33.3%)
Rhinorrhea	0/3 (0%)		2/9 (22.2%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Pruritis	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Rash	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Herpes zoster	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Vascular disorders
Heamoptysis	1/3 (33.3%)		0/9 (0%)		0/3 (0%)
Hot flush	0/3 (0%)		1/9 (11.1%)		0/3 (0%)
Hypertension	1/3 (33.3%)		1/9 (11.1%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.