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

NCT00199875 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LUD2002-022MSKCC IRB #: 05-031
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Carcinoma; Kidney Neoplasm; Renal Cancer; Kidney Cancer

Keywords

antibody; renal cell carcinoma; advanced renal cancer; cG250; ^90Y

Outcome Measures

Primary Outcomes (1)

• 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.

  Continuously for up to 5 months

Secondary Outcomes (2)

• Number of Patients Who Met Protocol-Specified Criteria to Receive ^90-Y-DOTA-cG250 Following ^111In-DOTA-cG250 Administration

  Up to 5 months

• Number of Patients With Samples Collected for Evaluation of Human Antichimeric Antibody

  Up to 6 months

Study Arms (5)

Cohort 1 (0.2 mCi/kg)

EXPERIMENTAL

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)

Cohort 2 (0.3 mCi/kg)

EXPERIMENTAL

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)

Cohort 3 (0.4 mCi/kg)

EXPERIMENTAL

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)

Cohort 4 (0.45 mCi/kg)

EXPERIMENTAL

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)

Cohort 5 (0.55 mCi/kg)

EXPERIMENTAL

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)

Interventions

Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250) DRUG

Patients received a single infusion of \^90Y-DOTA-cG250, with escalating doses administered to sequentially enrolled cohorts until MTD determination.

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

(212) 450-1539

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients were enrolled sequentially in cohorts of 3 to 6 patients to receive escalating doses of study treatment until determination of the MTD.

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: July 6, 2005
• Primary Completion: March 14, 2013
• Study Completion: March 14, 2013
• Last Updated: October 10, 2022
• Results First Posted: November 28, 2018

Record last verified: 2022-10

Locations

US (1)