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NCT00199875

Treatment of Patients With Advanced Renal Cancer With a Radiolabeled Antibody, Yttrium-90 Conjugated Chimeric G250

Completed Phase 1 Results posted Last updated 10 October 2022
What this trial tests

Phase 1 trial testing Yttrium-90 conjugated chimeric G250 (^90Y-DOTA-cG250) in Renal Cell Carcinoma in 18 participants. Completed in 14 March 2013.

Timeline
6 July 2005
Primary endpoint
14 March 2013
14 March 2013

Quick facts

Lead sponsorLudwig Institute for Cancer Research
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment18
Start date6 July 2005
Primary completion14 March 2013
Estimated completion14 March 2013
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Ludwig Institute for Cancer Research

Who can join

18 and older, any sex, with Renal Cell Carcinoma or Kidney Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Treatment-emergent Adverse Events Primary · Continuously for up to 5 months

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity (DLT) was defined as follows for the purposes of dose escalation: Grade 4 hematopoietic toxicity in excess of 5 days or Grade 3 or greater nonhematopoietic toxicity.

Any TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Maximum grade 1 TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)2
Cohort 2 (0.3 mCi/kg)2
Cohort 3 (0.4 mCi/kg)2
Cohort 4 (0.45 mCi/kg)1
Cohort 5 (0.55 mCi/kg)0
Maximum grade 2 TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)0
Cohort 2 (0.3 mCi/kg)1
Cohort 3 (0.4 mCi/kg)1
Cohort 4 (0.45 mCi/kg)0
Cohort 5 (0.55 mCi/kg)0
Maximum grade 3 TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)1
Cohort 2 (0.3 mCi/kg)0
Cohort 3 (0.4 mCi/kg)3
Cohort 4 (0.45 mCi/kg)1
Cohort 5 (0.55 mCi/kg)1
Maximum grade 4 TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)0
Cohort 2 (0.3 mCi/kg)0
Cohort 3 (0.4 mCi/kg)0
Cohort 4 (0.45 mCi/kg)1
Cohort 5 (0.55 mCi/kg)2
Treatment-related TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)2
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)5
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Serious TEAE
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)0
Cohort 2 (0.3 mCi/kg)0
Cohort 3 (0.4 mCi/kg)1
Cohort 4 (0.45 mCi/kg)1
Cohort 5 (0.55 mCi/kg)0
TEAE Leading to Treatment Discontinuation
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)0
Cohort 2 (0.3 mCi/kg)0
Cohort 3 (0.4 mCi/kg)0
Cohort 4 (0.45 mCi/kg)0
Cohort 5 (0.55 mCi/kg)0
Number of Patients Who Met Protocol-Specified Criteria to Receive ^90-Y-DOTA-cG250 Following ^111In-DOTA-cG250 Administration Secondary · Up to 5 months

In order to receive the therapeutic \^90Y-DOTA-cG250 injection on Day 8, 9, or 10, patients must have demonstrated tumor targeting to lesions \> 2 cm detected by CT scan and must not have exhibited the following characteristics following the nontherapeutic injection of \^111In-DOTA-cG250: excessive liver and/or spleen uptake; excessive uptake in the normal kidney; non-visualization of the cardiac blood pool in the first imaging set; whole body clearance half-life (t1/2) \< 1.5 days; serum t1/2 \< 2 days; rapid clearance of the radiopharmaceutical from the blood pool with prominent marrow uptak

GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Number of Patients With Samples Collected for Evaluation of Human Antichimeric Antibody Secondary · Up to 6 months

Blood samples were drawn for evaluation of the human antichimeric antibody (HACA) at screening, between Days 22 and 28, between Days 36 and 42, between Days 43 and 57 or at the end of study, and during long-term follow-up (approximately 12 weeks later). Serial dilutions were tested by the enzyme-linked immunosorbent assay (ELISA) using the "double antibody sandwich" technique and pretreatment serum as negative control.

Baseline
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Day 28
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Day 42
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)3
Cohort 5 (0.55 mCi/kg)3
Day 63
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)3
Cohort 2 (0.3 mCi/kg)3
Cohort 3 (0.4 mCi/kg)6
Cohort 4 (0.45 mCi/kg)2
Cohort 5 (0.55 mCi/kg)2
Long-term Follow-up
GroupValue95% CI
Cohort 1 (0.2 mCi/kg)0
Cohort 2 (0.3 mCi/kg)0
Cohort 3 (0.4 mCi/kg)0
Cohort 4 (0.45 mCi/kg)0
Cohort 5 (0.55 mCi/kg)1

Adverse events — posted to ClinicalTrials.gov

Time frame: All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 5 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 (0.2 mCi/kg)
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 2 (0.3 mCi/kg)
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 3 (0.4 mCi/kg)
Serious: 1/6 (17%)
Deaths: 0/6
Cohort 4 (0.45 mCi/kg)
Serious: 1/3 (33%)
Deaths: 0/3
Cohort 5 (0.55 mCi/kg)
Serious: 0/3 (0%)
Deaths: 0/3

Serious adverse events (4 terms)

ReactionSystemCohort 1 (0.2 mCi/kg)Cohort 2 (0.3 mCi/kg)Cohort 3 (0.4 mCi/kg)Cohort 4 (0.45 mCi/kg)Cohort 5 (0.55 mCi/kg)
Back painMusculoskeletal and connective tissue disorders
Respiratory tract haemorrhageRespiratory, thoracic and mediastinal disorders
HypercalcaemiaMetabolism and nutrition disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Other adverse events (47 terms — click to expand)

ReactionSystemCohort 1 (0.2 mCi/kg)Cohort 2 (0.3 mCi/kg)Cohort 3 (0.4 mCi/kg)Cohort 4 (0.45 mCi/kg)Cohort 5 (0.55 mCi/kg)
HyperglycaemiaMetabolism and nutrition disorders
HaemoglobinInvestigations
Platelet countInvestigations
Blood creatinineInvestigations
Blood alkaline phosphataseInvestigations
White blood cell countInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
LymphopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
Neutrophil countInvestigations
International normalised ratioInvestigations
Alanine aminotransferaseInvestigations
NauseaGastrointestinal disorders
HyperkalaemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Aspartate aminotransferaseInvestigations
AlopeciaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
HypersensitivityImmune system disorders
Prothrombin timeInvestigations
Back painMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
AmylaseInvestigations
HypernatraemiaMetabolism and nutrition disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
VomitingGastrointestinal disorders
Mucosal inflammationGeneral disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
Blood bicarbonate decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ChillsGeneral disorders
Oedema peripheralGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders

Most-reported serious reactions: Back pain, Respiratory tract haemorrhage, Hypercalcaemia, Musculoskeletal chest pain.

Data from ClinicalTrials.gov NCT00199875 adverse events section.

Sponsor's own description

This was a Phase 1, open-label, dose-escalation study of yttrium-90 conjugated chimeric G250 (\^90Y-DOTA-cG250) in patients with advanced, measurable clear cell renal cell carcinoma (RCC). Study objectives were to determine the safety, targeting, and dosimetry of \^90Y-DOTA-cG250, using indium-111 conjugated chimeric G250 (\^111In-DOTA-cG250) as a surrogate, as well as to evaluate the immunogenicity of cG250.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Application of monoclonal antibody G250 recognizing carbonic anhydrase IX in renal cell carcinoma.
    Oosterwijk-Wakka JC, Boerman OC, Mulders PF, Oosterwijk E. · · 2013 · cited 53× · PMID 23759990 · DOI 10.3390/ijms140611402
  2. Progress of molecular targeted therapies for advanced renal cell carcinoma.
    Conti A, Santoni M, Amantini C, Burattini L, et al · · 2013 · cited 31× · PMID 24093097 · DOI 10.1155/2013/419176
  3. Targeted therapy for renal cell carcinoma: The next lap.
    Kanesvaran R, Tan MH. · · 2014 · cited 22× · PMID 24737951 · DOI 10.4103/1477-3163.127638
  4. Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.
    Sharma S, Pandey MK. · · 2023 · cited 13× · PMID 37895931 · DOI 10.3390/ph16101460

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00199875.

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