Clinical trial NCT02002312: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2013-12-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Tumor response
timeFrame: 12 weeks
Secondary outcomes:
measure: Progression free survival
timeFrame: 3 years
measure: Toxicity
timeFrame: up to 14 weeks after last therapeutic infusion
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
Study officials:
affiliation: Department of Nuclear Medicine, Radboud University Medical Center Nijmegen
name: W. J. Oyen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Urology, Radboud University Medical Center Nijmegen
name: P. F. Mulders, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.