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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

111-In-DOTA-cG250

177-Lu-DOTA-cG250

About this trial

This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma (CCRCC), Lutetium-177, 177-Lu, cG250, DOTA-cG250, Monoclonal Antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

University Medical Center Nijmegen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

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

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

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

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

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

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

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m^2 of 177-Lu.

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m^2 of 177-Lu.

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m^2 of 177-Lu.

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m^2 of 177-Lu.

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m^2 of 177-Lu.

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m^2 of 177-Lu.

Outcomes

Primary Outcome Measures

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.

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).

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.

Secondary Outcome Measures

Number of Subjects With Best Overall Tumor Response

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.

Full Information

NCT ID

NCT00142415

First Posted

August 31, 2005

Last Updated

October 3, 2022

Sponsor

Ludwig Institute for Cancer Research

Collaborators

Radboud University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00142415

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

February 2005 (undefined)

Primary Completion Date

January 2011 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ludwig Institute for Cancer Research

Collaborators

Radboud University Medical Center

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Renal Cell Carcinoma

Keywords

Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma (CCRCC), Lutetium-177, 177-Lu, cG250, DOTA-cG250, Monoclonal Antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m^2 of 177-Lu.

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m^2 of 177-Lu.

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m^2 of 177-Lu.

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m^2 of 177-Lu.

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m^2 of 177-Lu.

Arm Title

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

Arm Type

Experimental

Arm Description

Subjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m^2 of 177-Lu.

Intervention Type

Drug

Intervention Name(s)

111-In-DOTA-cG250

Other Intervention Name(s)

cG250, DOTA-cG250, cG250-In111

Intervention Description

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

Intervention Name(s)

177-Lu-DOTA-cG250

Other Intervention Name(s)

cG250, DOTA-cG250, cG200-Lu177

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Subjects With Treatment-emergent Adverse Events

Description

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.

Time Frame

Up to 1 year

Title

Number of Subjects With Dose-limiting Toxicity (DLT) During Cycle 1

Description

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).

Time Frame

12 weeks

Title

Radiation Absorbed Doses by Organ for 177-Lu-cG250

Description

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.

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Number of Subjects With Best Overall Tumor Response

Description

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.

Time Frame

Up to 9 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

W.J.G. Oyen, MD

Organizational Affiliation

Department of Nuclear Medicine, University Medical Center Nijmegen

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

P.F.A. Mulders, MD

Organizational Affiliation

Department of Urology, University Medical Center Nijmegen

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Medical Center Nijmegen

City

Nijmegen

ZIP/Postal Code

6500HB

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data have been published

Citations:

PubMed Identifier

22980441

Citation

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.

Results Reference

result

PubMed Identifier

22159179

Citation

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.

Results Reference

result

Links:

URL

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

Description

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

Metastatic Renal Cell Carcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial