Safety Study With the Antibody, cG250, and Isotope, 124-Iodine, to Diagnose Patients With Renal Masses.

Pilot Study of Iodine-124 Labeled Chimeric G250 (124I-cG250) in Presurgical Patients With Renal Masses

The purpose of this study is to see if an antibody (cG250) attached to a radioactive substance (Iodine-124) safely detects clear cell renal cancer in patients with kidney tumors scheduled for surgery.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Clear Cell Renal Cell Carcinoma; Renal Cancer; Renal Cell Carcinoma (RCC); Renal Neoplasms; Cancer of Kidney; Neoplasms, Kidney
• Intervention / Treatment: Drug: 124-Iodine-cG250 (124I-cG250)

Detailed Description

Antibodies are proteins made by the immune system. They fight things that the body sees as foreign, such as bacteria and viruses. The body can also see cancer cells as foreign. When the body sees a foreign invader, it sends out antibodies that tag the invader. Once this happens, the immune system can work to destroy whatever the antibody has tagged.

Monoclonal antibodies are antibodies that can be made in the lab. They tag a portion of a cancer cell. Early monoclonal antibodies were made from antibodies grown in mice. They caused an antibody response in humans after one dose. Now they are more like human antibodies, and thus, do not produce the same reactions on repeated doses. These are called chimeric antibodies. The antibody we will use in this study is called chimeric G250 (cG250).

Recent research has shown that some antibodies can attach themselves to cancer cells, and that they bind to very few normal cells. This could help cancer treatment in two ways. One is that the body's own immune system might work to destroy tagged cancer cells. The other is that we can attach chemotherapy drugs or radioactive chemicals to the antibodies. These can then deliver treatment when the antibodies attach to the cancer cells.

This study is being done to test the tagging ability of cG250 to cancer cells. After you receive cG250, you will have a scan. The picture the scan produces will show where the antibody has collected inside the body. From this, it is possible to measure how well cG250 can detect kidney cancer. This is NOT a treatment for renal cancer. After your surgery, we will examine the tumor and other tissue to see how much of the antibody has attached to the tumor.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Presence of a renal mass.
2. Scheduled for surgical resection of renal mass.
3. Expected survival of at least 3 months.
4. Karnofsky performance scale ≥70.

5. The following laboratory results should be within the following limits within the last 4 weeks prior to study day 1:

   • Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L
   • Platelet count ≥ 100 x 10E9/L
   • Serum bilirubin ≤ 2.0 mg/dL
   • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
   • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
   • Serum creatinine ≤ 2.0 mg/dL
6. Pregnancy Test to be performed on female patients of childbearing potential within 24-48 hours before administration of radioactive material.
7. Recovered from toxicity of any prior therapy.
8. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Intercurrent medical condition that may limit the amount of antibody to be administered.
2. Intercurrent medical condition that renders the patient ineligible for surgery.
3. New York Heart Association Class III/IV cardiac disease.
4. History of autoimmune hepatitis.
5. Chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to the first cG250 dose.
6. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
7. Lack of availability for immunological and clinical follow-up assessments.
8. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
9. Women who are pregnant or breastfeeding.
10. Allergy to iodine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 124I-cG250; Patients who were scheduled for surgical resection of renal masses received a single intravenous (IV) dose of 10 mg of 5 milliCurie (mCi) /10 mg 124I-cG250. Patients underwent Positron-Emission Tomography/Computed Tomography (PET/CT) imaging of the whole body on at least 2 occasions: once following injection and once immediately prior to surgical resection. Patients were scheduled for surgical resection of their renal masses on day 8.

Drug: 124-Iodine-cG250 (124I-cG250)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value (PPV) of 124I-cG250 Based on Positron-Emission Tomography/Computed Tomography (PET/CT) Imaging in the Detection of Clear Cell Renal Cell Carcinoma (RCC) Compared to Pathology of Tumor Mass at Surgical Resection.	Patients were listed as PET-positive based on a tumor to nontumor radioactive uptake ratio of > 3 and PET-negative if less than or equal to 3. The resected renal mass (tumor) was subjected to pathological evaluation, and a diagnosis of clear cell RCC or non-clear cell RCC was made. PPV is the proportion of patients with a positive PET scan who actually have the disease based on pathology. Patients who have a positive PET scan on imaging and clear cell RCC on pathology will be considered true-positives. Patients who have negative PET scans on imaging and non-clear cell RCC on pathology will be considered true-negatives. Patients with positive PET scans on imaging and non-clear cell RCC on pathology will be considered false positives and those with clear cell RCC on pathology but negative PET scans on imaging will be considered false negatives.	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative Predictive Value (NPV) of 124I-cG250 Based on Positron-Emission Tomography/Computed Tomography (PET/CT) Imaging in the Detection of Clear Cell Renal Cell Carcinoma (RCC) Compared to Pathology of Tumor Mass at Surgical Resection.	Patients were listed as PET-positive based on a tumor to nontumor radioactive uptake ratio of > 3 and PET-negative if less than or equal to 3. The resected renal mass (tumor) was subjected to pathological evaluation, and a diagnosis of clear cell RCC or non-clear cell RCC was made. NPV is the ratio of participants who do not have clear cell RCC to all those who had negative PET scans. Patients who have a positive PET scan on imaging and clear cell RCC on pathology will be considered true-positives. Patients who have a negative PET scan on imaging and do not have clear cell RCC on pathology will be considered true-negatives. Patients with a positive PET scan on imaging and do not have clear cell RCC on pathology will be considered false positives and those with clear cell RCC on pathology but negative PET scans on imaging will be considered false negatives.	8 days
Sensitivity of 124I-cG250 Based on Positron-Emission Tomography/Computed Tomography (PET/CT) Imaging in the Detection of Clear Cell Renal Cell Carcinoma (RCC) Compared to Pathology of Tumor Mass at Surgical Resection.	Patients were listed as PET-positive based on a tumor to nontumor radioactive uptake ratio of > 3 and PET-negative if less than or equal to 3. The resected renal mass (tumor) was subjected to pathological evaluation, and a diagnosis of clear cell RCC or non-clear cell RCC was made. Sensitivity is defined as the ratio of the proportion of the patients who have clear cell RCC based on pathology and whose PET scans are positive over the number of patients with clear cell RCC. Patients who have a positive PET scan on imaging and clear cell RCC on pathology will be considered true-positives. Patients who have a negative PET scan on imaging and do not have clear cell RCC on pathology will be considered true-negatives. Patients with a positive PET scan on imaging and do not have clear cell RCC on pathology will be considered false positives and those with clear cell RCC on pathology but negative PET scans on imaging will be considered false negatives.	8 days
Specificity of 124I-cG250 Based on Positron-Emission Tomography/Computed Tomography (PET/CT) Imaging in the Detection of Clear Cell Renal Cell Carcinoma (RCC) Compared to Pathology of Tumor Mass at Surgical Resection.	Patients were listed as PET-positive based on a tumor to nontumor radioactive uptake ratio of > 3 and PET-negative if less than or equal to 3. The resected renal mass (tumor) was subjected to pathological evaluation, and a diagnosis of clear cell RCC or non-clear cell RCC was made. Specificity is defined as the number of patients with non-clear cell RCC correctly classified divided by all non-clear cell RCC patients. Patients who have a positive PET scan on imaging and clear cell RCC on pathology will be considered a true-positive. Patients who have a negative PET scan on imaging and do not have clear cell RCC on pathology will be considered true negatives. Patients with a positive PET scan on imaging and do not have clear cell RCC on pathology will be considered false positives and those with clear cell RCC on pathology but negative PET scans on imaging will be considered false negatives.	8 days

Collaborators and Investigators

• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Chaitanya R Divgi, MD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Pual Russo, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Divgi CR, Pandit-Taskar N, Jungbluth AA, Reuter VE, Gonen M, Ruan S, Pierre C, Nagel A, Pryma DA, Humm J, Larson SM, Old LJ, Russo P. Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncol. 2007 Apr;8(4):304-10. doi: 10.1016/S1470-2045(07)70044-X.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2005
• Primary Completion (ACTUAL): March 1, 2006
• Study Completion (ACTUAL): May 29, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (ESTIMATE): September 20, 2005

Study Record Updates

• Last Update Posted (ACTUAL): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: antibody; Kidney Cancer; Renal Cancer; Neoplasms, Kidney; cG250; Iodine 124
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: LUD2002-003; MSKCC IRB#: 05-004 (OTHER: MSKCC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No