Journal article
Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma
Clinical cancer research, Vol.31(7), pp.1204-1211
04/01/2025
DOI: 10.1158/1078-0432.CCR-24-3234
PMCID: PMC11961314
PMID: 39879383
Abstract
Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC.
Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment). Escalating dose levels of SLM (2500, 3000 and 4000 μg) were administered orally twice daily for 14 days, then once daily concurrently with axitinib 5 mg twice daily using a 3+3 design in Phase I. Patients were treated at the 4000 μg dose level in the expansion cohort to obtain preliminary estimates of efficacy.
No dose limiting toxicities occurred at the 4000 μg SLM dose level. Among the 27 patients treated with 4000 μg of SLM, the overall response rate was 55.6%, median duration of response was 18.4 months, median progression-free survival was 14.8 months, and median overall survival was 19.6 months. Preliminary results have shown that plasma selenium concentrations, inhibition of TGF-β1 and stabilization of tumor vasculature by SLM are time dependent.
SLM (4000 μg) in sequential combination with axitinib is well tolerated with encouraging efficacy.
Details
- Title: Subtitle
- Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma
- Creators
- Yousef Zakharia - University of Iowa Hospitals and ClinicsRyan J Reis - University of IowaMatthew R Kroll - University of Iowa Hospitals and ClinicsAseel O Rataan - University of IowaSrija Manchkanti - University of IowaBilal Rahim - University of IowaRohan Garje - Baptist Health South FloridaUmang Swami - Huntsman Cancer InstituteSarah L Mott - University of IowaK D Zamba - University of Iowa, BiostatisticsJessica C Sieren - University of IowaAliasger K Salem - University of IowaYoucef Rustum - Roswell Park Comprehensive Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.31(7), pp.1204-1211
- DOI
- 10.1158/1078-0432.CCR-24-3234
- PMID
- 39879383
- PMCID
- PMC11961314
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- Pfizer (Davis): P30 CA086862 Pipeline Acceleration for Cancer Therapeutics initiative by Holden Comprehensive Cancer Center, NCIRock "n" Ride fundraiser, Washington, IAPfizerSabinsa: P42 ES013661 NIHIowa Superfund Research Program grant
This trial was supported by Pipeline Acceleration for Cancer Therapeutics initiative by Holden Comprehensive Cancer Center, NCI P30 CA086862, and Rock "n" Ride fundraiser, Washington, IA. The expansion cohort is being supported by funding from Pfizer. S.L. Mott was supported by Sabinsa. Basic science research on selenium was supported by NIH P42 ES013661 and Iowa Superfund Research Program grant.
- Language
- English
- Electronic publication date
- 01/29/2025
- Date published
- 04/01/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Research Administration; Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
- Record Identifier
- 9984781277002771
Metrics
111 Record Views