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

NCT ID: NCT00142415

Last Updated: 2022-10-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-02-28

Study Completion Date

2011-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Metastatic Renal Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

111-In-DOTA-cG250

Intervention Type DRUG

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.

177-Lu-DOTA-cG250

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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cG250 DOTA-cG250 cG250-In111 cG250 DOTA-cG250 cG200-Lu177

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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W.J.G. Oyen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nuclear Medicine, University Medical Center Nijmegen

P.F.A. Mulders, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, University Medical Center Nijmegen

Locations

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University Medical Center Nijmegen

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type RESULT
PMID: 22980441 (View on PubMed)

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.

Reference Type RESULT
PMID: 22159179 (View on PubMed)

Related Links

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http://jnm.snmjournals.org/content/53/1/82.long

Stillebroer et al. J Nucl Med 2012; 53(1):82-89

Other Identifiers

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LUD2003-006

Identifier Type: -

Identifier Source: org_study_id

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