Phase I/II Dose-escalation Study of Lutetium-177-labeled cG250 in Patients With Advanced Renal Cancer

October 3, 2022 updated by: Ludwig Institute for Cancer Research

Phase I/II Study of Increasing Doses of Lutetium-177 Labeled Chimeric Monoclonal Antibody cG250 (177^Lu-DOTA-cG250) in Patients With Advanced Renal Cancer

This was a Phase I/II, single-center, dose-escalation study. 177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250 (177-Lu-DOTA-cG250) was administered at a starting dose of 30 mCi/m^2 of 177-Lu (fixed dose of 10 mg cG250) and escalated in increments of 10 mCi/m^2 of 177-Lu in sequentially enrolled cohorts according to a standard 3 + 3 design until determination of the maximum tolerated dose (MTD). The primary objectives were to determine the safety, targeting, and dosimetry of 177-Lu-DOTA-cG250 in subjects with advanced renal cell carcinoma. The secondary objective was measurement of tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Prior to administration of 177-Lu-DOTA-cG250, subjects received 5 mCi/10 mg of the 111-Indium-DOTA-cG250 (111-In-DOTA-cG250) antibody (an imaging dose). Whole body and blood measurements of radioactivity were obtained on at least 3 occasions for 1 week to determine targeting and dosimetry. If at least one known and evaluable metastatic lesion was visualized with 111-In-DOTA-cG250, a single dose of therapeutic 177-Lu-DOTA-cG250 was administered the following week. In the absence of disease progression and after recovery from toxicity, subjects may have been retreated no sooner than 12 weeks after the previous treatment with a dose of no more than 75% of the previous dose, for a total of not more than 3 treatments. Only subjects with normal pharmacokinetics on the diagnostic 111-In-DOTA-cG250 study (indicative of human anti-chimeric antibody [HACA] negativity) were eligible for re-treatment.

Subjects in the initial cohort were enrolled sequentially to receive 30 mCi/m^2 of 177-Lu-DOTA-cG250 (fixed dose of 10 mg cG250). In the absence of a dose-limiting toxicity, the dose was escalated in each subsequent cohort in 10 mCi/m^2 increments of 177-Lu. At least 3 subjects per dose level were followed for up to 12 weeks with imaging, biochemical, and hematologic tests. Safety was monitored continuously throughout the study.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6500HB
        • University Medical Center Nijmegen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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. Subjects with proven advanced and progressive renal cell carcinoma (RCC) of the clear cell type.
  2. At least one evaluable lesion < 5 cm.
  3. Karnofsky performance status ≥ 70%.

  4. Laboratory values obtained < 14 days prior to registration:

    • White blood cells (WBC) ≥ 3.5 × 10^9/L
    • Platelet count ≥ 100 × 10^9/L
    • Hemoglobin ≥ 6 mmol/L
    • Total bilirubin ≤ 2 × upper limit of normal (ULN)
    • Aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN (< 5 × ULN if liver metastases present)
    • Serum creatinine ≤ 2 × ULN
  5. Negative pregnancy test for women of childbearing potential (urine or serum).
  6. Age over 18 years.
  7. Ability to provide written informed consent.

Exclusion Criteria:

  1. Known metastases to the brain.
  2. Untreated hypercalcemia.
  3. Metastatic disease limited to the bone.
  4. Pre-exposure to murine/chimeric antibody therapy.
  5. Chemotherapy, external beam radiation or immunotherapy within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures was allowed, when unirradiated, evaluable lesions were present elsewhere.
  6. Cardiac disease with New York Heart Association classification of III or IV.
  7. Subjects who were pregnant, nursing or of reproductive potential and were not practicing an effective method of contraception.
  8. Any unrelated illness, e.g., active infection, inflammation, medical condition or laboratory abnormality, that in the judgement of the investigator would have significantly affected the subject's clinical status.
  9. Life expectancy < 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 3, 50 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 4, 60 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 5, 70 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 6, 65 mCi/m^2 177-Lu-DOTA-cG250
Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m^2 of 177-Lu.
Drug: 111-In-DOTA-cG250
On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Treatment-emergent Adverse Events
Time Frame: Up to 1 year
Toxicity was graded in accordance with the NCI CTCAE version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.
Up to 1 year
Number of Subjects With Dose-limiting Toxicity (DLT) During Cycle 1
Time Frame: 12 weeks
Subjects were monitored for AEs for ≥ 8 weeks after the last infusion of 177-Lu-DOTA-cG250 before dose escalation could be implemented. Toxicity was graded in accordance with the NCI CTCAE version 3.0. DLT was defined as the following treatment-related events: ≥ Grade 3 non-hematologic toxicity; ≥ Grade 4 hematologic toxicity (platelets < 25 × 10^9/L or leukocytes < 1.0 × 10^9/L) that persisted for > 4 weeks except anemia; thrombocytopenia < 10 × 10^9/L; clinically relevant myelotoxicity that required hospitalization and/or blood product transfusion (e.g., uncontrolled bleeding, infections that had to be treated clinically).
12 weeks
Radiation Absorbed Doses by Organ for 177-Lu-cG250
Time Frame: 12 weeks
After each 177-Lu-cG250 administration, 3 whole-body scintigrams were acquired (directly after injection and 2-4 days and 5-7 days post-injection) and blood samples were drawn at 5, 30, 60, and 120 min, 2-4 days, and 5-7 days post-infusion. Estimated radiation absorbed doses were calculated according to the Medical Internal Radiation Dose scheme, which permits estimation of the factors required to calculate dose to one organ attributable to a source in another organ.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Best Overall Tumor Response
Time Frame: Up to 9 months
Tumor responses were evaluated using computed tomography and categorized according to RECIST v1.0 at baseline and at the end of every cycle (every 12 weeks) or after recovery from toxicity. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Up to 9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ludwig Institute for Cancer Research

Collaborators

Radboud University Medical Center

Investigators

  • Principal Investigator: W.J.G. Oyen, MD, Department of Nuclear Medicine, University Medical Center Nijmegen
  • Principal Investigator: P.F.A. Mulders, MD, Department of Urology, University Medical Center Nijmegen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

August 31, 2005

First Submitted That Met QC Criteria

August 31, 2005

First Posted (Estimate)

September 2, 2005

Study Record Updates

Last Update Posted (Actual)

October 28, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LUD2003-006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data have been published

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Renal Cell Carcinoma

Clinical Trials on 111-In-DOTA-cG250

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tunisia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe