Treatment of Patients With Advanced Renal Cancer With a Radiolabeled Antibody, Yttrium-90 Conjugated Chimeric G250

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00199875
• Collaborator: Memorial Sloan Kettering Cancer Center (Other)
• Enrollment: 18
• Location: 1
• Arms: 5
• Actual Duration (Months): 92.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma; Kidney Neoplasm; Renal Cancer; Kidney Cancer	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250)	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Patients were enrolled sequentially in cohorts of 3 to 6 patients to receive escalating doses of study treatment until determination of the MTD.Patients were enrolled sequentially in cohorts of 3 to 6 patients to receive escalating doses of study treatment until determination of the MTD.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cohort Study of Increasing Doses of Yttrium-90 Conjugated to Chimeric Monoclonal Antibody cG250 (^90Y-DOTA-cG250) in Patients With Advanced Renal Cancer
• Actual Study Start Date: Jul 6, 2005
• Actual Primary Completion Date: Mar 14, 2013
• Actual Study Completion Date: Mar 14, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (0.2 mCi/kg) 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.	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250); Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.
Experimental: Cohort 2 (0.3 mCi/kg) 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.	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250); Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.
Experimental: Cohort 3 (0.4 mCi/kg) 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.	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250); Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.
Experimental: Cohort 4 (0.45 mCi/kg) 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.	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250); Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.
Experimental: Cohort 5 (0.55 mCi/kg) 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.	Drug: Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250); Patients received a single infusion of ^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment-emergent Adverse Events [Continuously for up to 5 months]

   Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity (DLT) was defined as follows for the purposes of dose escalation: Grade 4 hematopoietic toxicity in excess of 5 days or Grade 3 or greater nonhematopoietic toxicity.

Secondary Outcome Measures

1. Number of Patients Who Met Protocol-Specified Criteria to Receive ^90-Y-DOTA-cG250 Following ^111In-DOTA-cG250 Administration [Up to 5 months]

   In order to receive the therapeutic ^90Y-DOTA-cG250 injection on Day 8, 9, or 10, patients must have demonstrated tumor targeting to lesions > 2 cm detected by CT scan and must not have exhibited the following characteristics following the nontherapeutic injection of ^111In-DOTA-cG250: excessive liver and/or spleen uptake; excessive uptake in the normal kidney; non-visualization of the cardiac blood pool in the first imaging set; whole body clearance half-life (t1/2) < 1.5 days; serum t1/2 < 2 days; rapid clearance of the radiopharmaceutical from the blood pool with prominent marrow uptake on the first image.

2. Number of Patients With Samples Collected for Evaluation of Human Antichimeric Antibody [Up to 6 months]

   Blood samples were drawn for evaluation of the human antichimeric antibody (HACA) at screening, between Days 22 and 28, between Days 36 and 42, between Days 43 and 57 or at the end of study, and during long-term follow-up (approximately 12 weeks later). Serial dilutions were tested by the enzyme-linked immunosorbent assay (ELISA) using the "double antibody sandwich" technique and pretreatment serum as negative control.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. All patients must have had histologically proven clear cell renal carcinoma.

2. Age ≥ 18 years. Children were not enrolled because clear cell renal cancer is rarely seen in children.

3. All patients must have had a clinical presentation consistent with metastatic renal carcinoma.

4. Patients must have had bidimensionally measurable disease by conventional imaging methods including radiography, ultrasound, CT, or other anatomic imaging modalities. Lesions seen on skeletal scintigraphy alone were not considered measurable.

5. Female patients of childbearing age were required to have a negative pregnancy test carried out the day of and prior to receiving therapy, and were asked to use effective contraception during the study.

6. All patients must have been ambulatory with a Karnofsky Performance Status of at least

8. The following laboratory results within the last 2 weeks prior to study Day 1:

• serum creatinine ≤ 2.0 mg/dL

• serum bilirubin (total) ≤ 2.0 mg/dL

• aspartate aminotransferase (AST) ≤ 2.5 × the upper limit of normal (ULN)

• alanine aminotransferase (ALT) ≤ 2.5 × ULN

• white blood cell (WBC) count ≥ 3500/mm^3

• platelet count ≥ 100,000/mm^3

• prothrombin time ≤ 1.3 × control

1. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Significant prior radiotherapy (> 30 Gy) to the entire pelvis and/or lumbosacral spine.

2. Clinically significant cardiac disease (New York Heart Association Class [III/IV]).

3. Serious infection requiring treatment with antibiotics, or other serious illness.

4. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to study agent administration.

5. Survival expectancy of less than 12 weeks.

6. Patients with central nervous system (CNS) involvement were excluded under the following criteria:

• Brain metastasis, except for stable disease over 3 months.

• Untreated brain metastasis.

• Evidence of progression of neurologic CNS involvement within 3 months prior to entering the protocol.

1. Hypercalcemia > 12.5 mg/100 mL or symptomatic.

2. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.

3. Lack of availability of the patient for clinical and laboratory follow-up assessment.

4. Patients known to have hepatobiliary disease and/or human immunodeficiency virus/acquired immune deficiency syndrome.

5. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

6. Pregnancy or breastfeeding.

7. Refusal or inability to use effective means of contraception in men or women of childbearing potential.

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
• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Steven Larson, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Neeta Pandit-Taskar, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Joseph O'Donoghue, PhD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Robert Motzer, 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: NCT00199875
• Other Study ID Numbers: LUD2002-022; MSKCC IRB #: 05-031
• First Posted: Sep 20, 2005
• Last Update Posted: Nov 28, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: antibody; renal cell carcinoma; advanced renal cancer; cG250; ^90Y
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms

Study Results

Participant Flow

Arm/Group Title	Cohort 1 (0.2 mCi/kg)	Cohort 2 (0.3 mCi/kg)	Cohort 3 (0.4 mCi/kg)	Cohort 4 (0.45 mCi/kg)	Cohort 5 (0.55 mCi/kg)
Arm/Group Description	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	3	3	6	3	3
COMPLETED	3	3	6	3	2
NOT COMPLETED	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Cohort 1 (0.2 mCi/kg)	Cohort 2 (0.3 mCi/kg)	Cohort 3 (0.4 mCi/kg)	Cohort 4 (0.45 mCi/kg)	Cohort 5 (0.55 mCi/kg)	Total
Arm/Group Description	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.	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	3	3	6	3	3	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.7 (9.2)	64.7 (4.9)	62.7 (7.9)	63.7 (6.8)	63.0 (5.9)	63.7 (7.3)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 33.3%	3 50%	0 0%	2 66.7%	7 38.9%
Male	2 66.7%	2 66.7%	3 50%	3 100%	1 33.3%	11 61.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	3 100%	6 100%	3 100%	3 100%	18 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 5.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 5.6%
White	3 100%	3 100%	6 100%	2 66.7%	2 66.7%	16 88.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	3 100%	6 100%	3 100%	3 100%	18 100%
Karnofsky Performance Status (Count of Participants)
70	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 5.6%
80	1 33.3%	0 0%	1 16.7%	0 0%	3 100%	5 27.8%
90	2 66.7%	2 66.7%	3 50%	2 66.7%	0 0%	9 50%
100	0 0%	0 0%	1 16.7%	1 33.3%	0 0%	2 11.1%
Missing	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 5.6%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment-emergent Adverse Events
Description	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity (DLT) was defined as follows for the purposes of dose escalation: Grade 4 hematopoietic toxicity in excess of 5 days or Grade 3 or greater nonhematopoietic toxicity.
Time Frame	Continuously for up to 5 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Arm/Group Title	Cohort 1 (0.2 mCi/kg)	Cohort 2 (0.3 mCi/kg)	Cohort 3 (0.4 mCi/kg)	Cohort 4 (0.45 mCi/kg)	Cohort 5 (0.55 mCi/kg)
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	3	6	3	3
Any TEAE	3 100%	3 100%	6 100%	3 100%	3 100%
Maximum grade 1 TEAE	2 66.7%	2 66.7%	2 33.3%	1 33.3%	0 0%
Maximum grade 2 TEAE	0 0%	1 33.3%	1 16.7%	0 0%	0 0%
Maximum grade 3 TEAE	1 33.3%	0 0%	3 50%	1 33.3%	1 33.3%
Maximum grade 4 TEAE	0 0%	0 0%	0 0%	1 33.3%	2 66.7%
Treatment-related TEAE	2 66.7%	3 100%	5 83.3%	3 100%	3 100%
Serious TEAE	0 0%	0 0%	1 16.7%	1 33.3%	0 0%
TEAE Leading to Treatment Discontinuation	0 0%	0 0%	0 0%	0 0%	0 0%
TEAE Meeting DLT Criteria	0 0%	0 0%	1 16.7%	0 0%	2 66.7%

2. Secondary Outcome

Title	Number of Patients Who Met Protocol-Specified Criteria to Receive ^90-Y-DOTA-cG250 Following ^111In-DOTA-cG250 Administration
Description	In order to receive the therapeutic ^90Y-DOTA-cG250 injection on Day 8, 9, or 10, patients must have demonstrated tumor targeting to lesions > 2 cm detected by CT scan and must not have exhibited the following characteristics following the nontherapeutic injection of ^111In-DOTA-cG250: excessive liver and/or spleen uptake; excessive uptake in the normal kidney; non-visualization of the cardiac blood pool in the first imaging set; whole body clearance half-life (t1/2) < 1.5 days; serum t1/2 < 2 days; rapid clearance of the radiopharmaceutical from the blood pool with prominent marrow uptake on the first image.
Time Frame	Up to 5 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Arm/Group Title	Cohort 1 (0.2 mCi/kg)	Cohort 2 (0.3 mCi/kg)	Cohort 3 (0.4 mCi/kg)	Cohort 4 (0.45 mCi/kg)	Cohort 5 (0.55 mCi/kg)
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	3	6	3	3
Count of Participants [Participants]	3 100%	3 100%	6 100%	3 100%	3 100%

3. Secondary Outcome

Title	Number of Patients With Samples Collected for Evaluation of Human Antichimeric Antibody
Description	Blood samples were drawn for evaluation of the human antichimeric antibody (HACA) at screening, between Days 22 and 28, between Days 36 and 42, between Days 43 and 57 or at the end of study, and during long-term follow-up (approximately 12 weeks later). Serial dilutions were tested by the 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

The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Arm/Group Title	Cohort 1 (0.2 mCi/kg)	Cohort 2 (0.3 mCi/kg)	Cohort 3 (0.4 mCi/kg)	Cohort 4 (0.45 mCi/kg)	Cohort 5 (0.55 mCi/kg)
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	3	6	3	3
Baseline	3 100%	3 100%	6 100%	3 100%	3 100%
Day 28	3 100%	3 100%	6 100%	3 100%	3 100%
Day 42	3 100%	3 100%	6 100%	3 100%	3 100%
Day 63	3 100%	3 100%	6 100%	2 66.7%	2 66.7%
Long-term Follow-up	0 0%	0 0%	0 0%	0 0%	1 33.3%

Adverse Events

Time Frame	All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 5 months.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTC (version 3.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.
Arm/Group Title	Cohort 1 (0.2 mCi/kg)		Cohort 2 (0.3 mCi/kg)		Cohort 3 (0.4 mCi/kg)		Cohort 4 (0.45 mCi/kg)		Cohort 5 (0.55 mCi/kg)
Arm/Group Description	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.		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.		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.		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.		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.
All Cause Mortality
	Cohort 1 (0.2 mCi/kg)		Cohort 2 (0.3 mCi/kg)		Cohort 3 (0.4 mCi/kg)		Cohort 4 (0.45 mCi/kg)		Cohort 5 (0.55 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)
Serious Adverse Events
	Cohort 1 (0.2 mCi/kg)		Cohort 2 (0.3 mCi/kg)		Cohort 3 (0.4 mCi/kg)		Cohort 4 (0.45 mCi/kg)		Cohort 5 (0.55 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Musculoskeletal chest pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (0.2 mCi/kg)		Cohort 2 (0.3 mCi/kg)		Cohort 3 (0.4 mCi/kg)		Cohort 4 (0.45 mCi/kg)		Cohort 5 (0.55 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Lymphopenia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		2/3 (66.7%)		3/3 (100%)
Gastrointestinal disorders
Nausea	0/3 (0%)		2/3 (66.7%)		1/6 (16.7%)		0/3 (0%)		2/3 (66.7%)
Diarrhoea	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Constipation	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/3 (0%)
Abdominal distension	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Abdominal pain upper	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Vomiting	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)
Abdominal pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/3 (66.7%)
General disorders
Fatigue	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		1/3 (33.3%)		3/3 (100%)
Mucosal inflammation	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Pyrexia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/3 (33.3%)
Chills	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Oedema peripheral	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Chest pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)
Immune system disorders
Hypersensitivity	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)
Infections and infestations
Urinary tract infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Investigations
Blood alkaline phosphatase	2/3 (66.7%)		0/3 (0%)		3/6 (50%)		1/3 (33.3%)		1/3 (33.3%)
Haemoglobin	2/3 (66.7%)		0/3 (0%)		5/6 (83.3%)		3/3 (100%)		3/3 (100%)
International normalised ratio	2/3 (66.7%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		1/3 (33.3%)
Platelet count	2/3 (66.7%)		3/3 (100%)		5/6 (83.3%)		3/3 (100%)		3/3 (100%)
Alanine aminotransferase	1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		2/3 (66.7%)
Blood creatinine	1/3 (33.3%)		2/3 (66.7%)		5/6 (83.3%)		1/3 (33.3%)		1/3 (33.3%)
Prothrombin time	1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/3 (33.3%)
White blood cell count	1/3 (33.3%)		2/3 (66.7%)		3/6 (50%)		2/3 (66.7%)		3/3 (100%)
Amylase	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Aspartate aminotransferase	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/3 (0%)
Blood bicarbonate decreased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Neutrophil count	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		3/3 (100%)
Metabolism and nutrition disorders
Hypoalbuminaemia	2/3 (66.7%)		0/3 (0%)		3/6 (50%)		1/3 (33.3%)		3/3 (100%)
Hyperglycaemia	1/3 (33.3%)		3/3 (100%)		6/6 (100%)		3/3 (100%)		3/3 (100%)
Hyperkalaemia	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)		2/3 (66.7%)
Hypernatraemia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)
Decreased appetite	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Hypophosphataemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Hyponatraemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/3 (66.7%)
Hypoglycaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)
Musculoskeletal chest pain	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)
Arthralgia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)
Nervous system disorders
Peripheral sensory neuropathy	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)
Dysarthria	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Psychiatric disorders
Anxiety	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/3 (33.3%)
Hypoxia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Increased upper airway secretion	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/3 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.