NCT00142415

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2005

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2005

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

August 31, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 2, 2005

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2011

Completed
6.2 years until next milestone

Results Posted

Study results publicly available

March 22, 2017

Completed
Last Updated

October 28, 2022

Status Verified

October 1, 2022

Enrollment Period

5.9 years

First QC Date

August 31, 2005

Results QC Date

November 30, 2016

Last Update Submit

October 3, 2022

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Advanced Renal Cell CarcinomaClear Cell Renal Cell Carcinoma (CCRCC)Lutetium-177177-LucG250DOTA-cG250Monoclonal Antibody

Outcome Measures

Primary Outcomes (3)

  • Number of Subjects With Treatment-emergent Adverse Events

    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

    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

    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 Outcomes (1)

  • Number of Subjects With Best Overall Tumor Response

    Up to 9 months

Study Arms (6)

Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Cohort 3, 50 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Cohort 4, 60 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Cohort 5, 70 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Cohort 6, 65 mCi/m^2 177-Lu-DOTA-cG250

EXPERIMENTAL

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-cG250Drug: 177-Lu-DOTA-cG250

Interventions

111-In-DOTA-cG250DRUG

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.

Also known as: cG250, DOTA-cG250, cG250-In111
Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250Cohort 3, 50 mCi/m^2 177-Lu-DOTA-cG250Cohort 4, 60 mCi/m^2 177-Lu-DOTA-cG250Cohort 5, 70 mCi/m^2 177-Lu-DOTA-cG250Cohort 6, 65 mCi/m^2 177-Lu-DOTA-cG250
177-Lu-DOTA-cG250DRUG

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.

Also known as: cG250, DOTA-cG250, cG200-Lu177
Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250Cohort 3, 50 mCi/m^2 177-Lu-DOTA-cG250Cohort 4, 60 mCi/m^2 177-Lu-DOTA-cG250Cohort 5, 70 mCi/m^2 177-Lu-DOTA-cG250Cohort 6, 65 mCi/m^2 177-Lu-DOTA-cG250

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subjects with proven advanced and progressive renal cell carcinoma (RCC) of the clear cell type.
  • At least one evaluable lesion \< 5 cm.
  • Karnofsky performance status ≥ 70%.
  • 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
  • Negative pregnancy test for women of childbearing potential (urine or serum).
  • Age over 18 years.
  • Ability to provide written informed consent.

You may not qualify if:

  • Known metastases to the brain.
  • Untreated hypercalcemia.
  • Metastatic disease limited to the bone.
  • Pre-exposure to murine/chimeric antibody therapy.
  • 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.
  • Cardiac disease with New York Heart Association classification of III or IV.
  • Subjects who were pregnant, nursing or of reproductive potential and were not practicing an effective method of contraception.
  • 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.
  • Life expectancy \< 6 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Medical Center Nijmegen

Nijmegen, 6500HB, Netherlands

Location

Related Publications (2)

  • Stillebroer AB, Boerman OC, Desar IM, Boers-Sonderen MJ, van Herpen CM, Langenhuijsen JF, Smith-Jones PM, Oosterwijk E, Oyen WJ, Mulders PF. Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma. Eur Urol. 2013 Sep;64(3):478-85. doi: 10.1016/j.eururo.2012.08.024. Epub 2012 Aug 21.

    PMID: 22980441RESULT

  • Stillebroer AB, Zegers CM, Boerman OC, Oosterwijk E, Mulders PF, O'Donoghue JA, Visser EP, Oyen WJ. Dosimetric analysis of 177Lu-cG250 radioimmunotherapy in renal cell carcinoma patients: correlation with myelotoxicity and pretherapeutic absorbed dose predictions based on 111In-cG250 imaging. J Nucl Med. 2012 Jan;53(1):82-9. doi: 10.2967/jnumed.111.094896. Epub 2011 Dec 12.

    PMID: 22159179RESULT

Related Links

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Jonathan Skipper PhD
Organization
Ludwig Institute for Cancer Research
jskipper@lcr.org
12124501539

Study Officials

  • 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

    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
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 31, 2005

First Posted

September 2, 2005

Study Start

February 1, 2005

Primary Completion

January 1, 2011

Study Completion

January 1, 2011

Last Updated

October 28, 2022

Results First Posted

March 22, 2017

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will share

Data have been published

Locations

NL(1)