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Phase II Study of Lutetium-177 Labeled Girentuximab in Patients With Advanced Renal Cancer

Primary Purpose

Metastatic Clear Cell Renal Cell Carcinoma

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Lu-177-DOTA-girentuximab
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion criteria:

  • Patients with proven advanced and progressive RCC of the clear cell type
  • Presence of RECIST v.1.1 evaluable lesions, all < 5 cm
  • Performance status: Karnofsky > 70 %
  • Laboratory values: • White blood cells (WBC) > 3.5 x 109/l • Platelet count > 150 x 109/l • Hemoglobin > 6 mmol/l • Total bilirubin < 2 x upper limit of normal (ULN) • ASAT, ALAT < 3 x ULN (< 5 x ULN if liver metastases present) • MDRD ≥ 40 ml/min
  • Negative pregnancy test for women of childbearing potential (urine or serum)
  • Age over 18 years
  • Written informed consent

Exclusion criteria:

  • Known or suspected CNS metastases including leptomeningeal metastases. History or clinical evidence of (CNS) metastases (unless they are previously-treated CNS metastases and patients meet all 3 of the following criteria: are asymptomatic, have had no evidence of active CNS metastases for ≥3 months prior to enrollment, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days)
  • Untreated hypercalcemia
  • Chemotherapy, external beam radiation, immunotherapy or angiogenesis inhibitors or mTOR inhibitors within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed , when unirradiated, evaluable lesions elsewhere are present.
  • Cardiac disease with New York Heart Association classification of III or IV
  • Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception
  • Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator will significantly affect patients' clinical status
  • Life expectancy shorter than 4 months.

Sites / Locations

  • Radboud University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lu-177-DOTA-girentuximab

Arm Description

Patients in receive 10 mg of girentuximab coupled to DOTA and labeled with 65 mCi/m2 of Lu-177 if targeting of In-111-DOTA-girentuximab is observed in at least 1 lesion. Patients may be retreated no sooner than 12 weeks after the prior treatment with a dose of no more than 75% of the previous dose, for a total of not more than three treatments.

Outcomes

Primary Outcome Measures

Tumor response
Evaluation according to RECIST criteria

Secondary Outcome Measures

Progression free survival
Progression free survival is defined as the time measured from the day of first administration of Lu-177-girentuximab to first progression or death, whichever comes first.
Toxicity
Toxicity defined by NCI Common Terminology Criteria for Adverse Events (CTCAE v3.0)

Full Information

First Posted
November 29, 2013
Last Updated
August 12, 2015
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02002312
Brief Title
Phase II Study of Lutetium-177 Labeled Girentuximab in Patients With Advanced Renal Cancer
Official Title
Phase II Study Of Lutetium-177 Labeled Chimeric Monoclonal Antibody Girentuximab (177Lu-DOTA-girentuximab) in Patients With Advanced Renal Cell Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To determine the efficacy of multiple doses Lutetium-177-DOTA-girentuximab in patients with advanced clear cell renal cell carcinoma using RECIST criteria.
Detailed Description
This is a Phase II study using Lu-177-DOTA-girentuximab for treatment of patients with advanced clear cell renal cell carcinoma. The trial requires 14 patients. CT scans will be carried out at baseline and after 12 weeks, for response assessment using RECIST criteria. Patients will initially receive 5 mCi/10 mg Indium-111-DOTA-girentuximab antibody (an imaging dose preceeding Lu-177-girentuximab treatment). Whole body and blood measurements of radioactivity will be obtained on at least three occasions for one week to determine targeting and dosimetry. Only if at least one known and evaluable metastatic lesion is visualized with In-111-DOTA-girentuximab, therapeutic Lu-177-DOTA- girentuximab will be administered the following week. In the absence of disease progression and after recovery from toxicity, patients may be retreated no sooner than 12 weeks after the prior treatment with a dose of no more than 75% of the previous dose, for a total of not more than three treatments. Only patients who have normal pharmacokinetics on the preceding diagnostic In-111-girentuximab study (indicative of human antichimeric antibodies (HACA) negativity) are eligible for retreatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Clear Cell Renal Cell Carcinoma
Keywords
Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma (ccRCC), Lutetium-177, Lu-177, girentuximab, cG250, Monoclonal Antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lu-177-DOTA-girentuximab
Arm Type
Experimental
Arm Description
Patients in receive 10 mg of girentuximab coupled to DOTA and labeled with 65 mCi/m2 of Lu-177 if targeting of In-111-DOTA-girentuximab is observed in at least 1 lesion. Patients may be retreated no sooner than 12 weeks after the prior treatment with a dose of no more than 75% of the previous dose, for a total of not more than three treatments.
Intervention Type
Drug
Intervention Name(s)
Lu-177-DOTA-girentuximab
Other Intervention Name(s)
Lu-177-DOTA-cG250
Intervention Description
Drug: In-111-DOTA-girentuximab At day 1, every patient received girentuximab at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of In-111. Drug: Lu-177-DOTA-girentuximab At day 8-10, every patient receives girentuximab at a dose of 10 mg coupled to DOTA and labeled with 65 mCi/m2 of Lu-177. If eligible, patients are retreated at a dose 75% of the previous dose, for a total of not more than three treatments.
Primary Outcome Measure Information:
Title
Tumor response
Description
Evaluation according to RECIST criteria
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival is defined as the time measured from the day of first administration of Lu-177-girentuximab to first progression or death, whichever comes first.
Time Frame
3 years
Title
Toxicity
Description
Toxicity defined by NCI Common Terminology Criteria for Adverse Events (CTCAE v3.0)
Time Frame
up to 14 weeks after last therapeutic infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Patients with proven advanced and progressive RCC of the clear cell type Presence of RECIST v.1.1 evaluable lesions, all < 5 cm Performance status: Karnofsky > 70 % Laboratory values: • White blood cells (WBC) > 3.5 x 109/l • Platelet count > 150 x 109/l • Hemoglobin > 6 mmol/l • Total bilirubin < 2 x upper limit of normal (ULN) • ASAT, ALAT < 3 x ULN (< 5 x ULN if liver metastases present) • MDRD ≥ 40 ml/min Negative pregnancy test for women of childbearing potential (urine or serum) Age over 18 years Written informed consent Exclusion criteria: Known or suspected CNS metastases including leptomeningeal metastases. History or clinical evidence of (CNS) metastases (unless they are previously-treated CNS metastases and patients meet all 3 of the following criteria: are asymptomatic, have had no evidence of active CNS metastases for ≥3 months prior to enrollment, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days) Untreated hypercalcemia Chemotherapy, external beam radiation, immunotherapy or angiogenesis inhibitors or mTOR inhibitors within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed , when unirradiated, evaluable lesions elsewhere are present. Cardiac disease with New York Heart Association classification of III or IV Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator will significantly affect patients' clinical status Life expectancy shorter than 4 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
W. J. Oyen, MD, PhD
Organizational Affiliation
Department of Nuclear Medicine, Radboud University Medical Center Nijmegen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
P. F. Mulders, MD, PhD
Organizational Affiliation
Department of Urology, Radboud University Medical Center Nijmegen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Medical Center
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
26706103
Citation
Muselaers CH, Boers-Sonderen MJ, van Oostenbrugge TJ, Boerman OC, Desar IM, Stillebroer AB, Mulder SF, van Herpen CM, Langenhuijsen JF, Oosterwijk E, Oyen WJ, Mulders PF. Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. Eur Urol. 2016 May;69(5):767-70. doi: 10.1016/j.eururo.2015.11.033. Epub 2015 Dec 23.
Results Reference
derived

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Phase II Study of Lutetium-177 Labeled Girentuximab in Patients With Advanced Renal Cancer

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