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

Primary Purpose

Renal Cell Carcinoma, Kidney Neoplasm, Renal Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250)
Sponsored by
Ludwig Institute for Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring antibody, renal cell carcinoma, advanced renal cancer, cG250, ^90Y

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: All patients must have had histologically proven clear cell renal carcinoma. Age ≥ 18 years. Children were not enrolled because clear cell renal cancer is rarely seen in children. All patients must have had a clinical presentation consistent with metastatic renal carcinoma. 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. 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. All patients must have been ambulatory with a Karnofsky Performance Status of at least 70. 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 Able and willing to give valid written informed consent. Exclusion Criteria: Significant prior radiotherapy (> 30 Gy) to the entire pelvis and/or lumbosacral spine. Clinically significant cardiac disease (New York Heart Association Class [III/IV]). Serious infection requiring treatment with antibiotics, or other serious illness. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to study agent administration. Survival expectancy of less than 12 weeks. 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. Hypercalcemia > 12.5 mg/100 mL or symptomatic. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study. Lack of availability of the patient for clinical and laboratory follow-up assessment. Patients known to have hepatobiliary disease and/or human immunodeficiency virus/acquired immune deficiency syndrome. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Pregnancy or breastfeeding. Refusal or inability to use effective means of contraception in men or women of childbearing potential.

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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 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.

Outcomes

Primary Outcome Measures

Number of Patients With Treatment-emergent Adverse Events
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

Number of Patients Who Met Protocol-Specified Criteria to Receive ^90-Y-DOTA-cG250 Following ^111In-DOTA-cG250 Administration
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.
Number of Patients With Samples Collected for Evaluation of Human Antichimeric Antibody
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.

Full Information

First Posted
September 13, 2005
Last Updated
October 3, 2022
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00199875
Brief Title
Treatment of Patients With Advanced Renal Cancer With a Radiolabeled Antibody, Yttrium-90 Conjugated Chimeric G250
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
July 6, 2005 (Actual)
Primary Completion Date
March 14, 2013 (Actual)
Study Completion Date
March 14, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma, Kidney Neoplasm, Renal Cancer, Kidney Cancer
Keywords
antibody, renal cell carcinoma, advanced renal cancer, cG250, ^90Y

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have had histologically proven clear cell renal carcinoma. Age ≥ 18 years. Children were not enrolled because clear cell renal cancer is rarely seen in children. All patients must have had a clinical presentation consistent with metastatic renal carcinoma. 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. 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. All patients must have been ambulatory with a Karnofsky Performance Status of at least 70. 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 Able and willing to give valid written informed consent. Exclusion Criteria: Significant prior radiotherapy (> 30 Gy) to the entire pelvis and/or lumbosacral spine. Clinically significant cardiac disease (New York Heart Association Class [III/IV]). Serious infection requiring treatment with antibiotics, or other serious illness. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to study agent administration. Survival expectancy of less than 12 weeks. 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. Hypercalcemia > 12.5 mg/100 mL or symptomatic. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study. Lack of availability of the patient for clinical and laboratory follow-up assessment. Patients known to have hepatobiliary disease and/or human immunodeficiency virus/acquired immune deficiency syndrome. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Pregnancy or breastfeeding. Refusal or inability to use effective means of contraception in men or women of childbearing potential.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Larson, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neeta Pandit-Taskar, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph O'Donoghue, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Motzer, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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