Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab

NCT05363631 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202104398
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety and effectiveness of Seleno-L Methionine (SLM) when combined with the standard dose and schedule of Axitinib and Pembrolizumab in patients who have locally advanced or metastatic clear cell renal cell carcinoma (ccRCC).

Conditions

Clear Cell Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma Metastatic

Outcome Measures

Primary Outcomes (2)

• Phase I - Dose limiting toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients

  From the initiation of treatment through three years

• Phase II - Objective Response Rate (ORR)

  ORR will be defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1

  From the initiation of treatment through three years

Secondary Outcomes (2)

• Progression-free survival (PFS)

  From the initiation of treatment through three years

• Overall survival (OS)

  From the initiation of treatment through three years

Study Arms (1)

Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab

EXPERIMENTAL

SLM only will be taken by mouth during a two-week run in period. Then patients will receive SLM and Axitinib drugs by mouth, and Pembrolizumab intravenously (IV), at the start of each 21 day cycle.

Drug: Selenomethionine (SLM); Drug: Axitinib; Drug: Pembrolizumab

Interventions

Selenomethionine (SLM) DRUG

Selenium (Se) is a natural element present in the earth's crust often in association with sulfur-containing compounds. Humans get their dietary requirements mainly from food. In this study Selenium will be administered in the chemical composition of selenomethionine (SLM)

Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab

Axitinib DRUG

Axitinib is a small molecule tyrosine kinase inhibitor.

Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is a type of immunotherapy

Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Written and voluntary informed consent.
• Histologically and radiologically confirmed locally advanced or metastatic ccRCC. Locally advanced is defined as non resectable in the opinion of the treating providers. Participants must be treatment naïve in metastatic setting. Prior immunotherapy treatment in adjuvant setting is allowed.
• \> 18 years of age
• At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1)-defined target lesion that has not been irradiated
• Eastern Cooperative Oncology Group performance status of 0 (fully active, able to carry on all pre-disease performance without restriction) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work).
• Renal function (creatinine level within normal institutional limit, or creatinine clearance \>15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).
• Liver function (AST/ALT \<3.0 X institutional upper limit of normal OR \< 5 x institutional upper limit of normal in cases of liver metastases; Total bilirubin ≤ 1.5 times ULN.)
• Adequate hematological lab values including
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 7.0 g/dL
• Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week before randomization/allocation.
• Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from the time of screening, throughout the total duration of the drug treatment, and during the 6 month post-drug washout period. See section 5.6 for full details.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Patients with a prior or concurrent malignancy whose natural history or treatment may have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Untreated metastases in the central nervous system.
• Pregnant or breastfeeding.
• Present use or anticipated need for cytochrome P450 (CYP) 3A4-inhibiting, CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and St. John's wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin).
• Myocardial infarction, uncontrolled angina, congestive heart failure, or cerebrovascular accident within previous 6 months. Participants with history of deep vein thrombosis or pulmonary embolism, at provider discretion.
• Major surgery within 4 weeks of starting study treatment.
• Patients with HIV infection with CD4+ T-cell (CD4+) counts \< 350 cells/uL
• Patients with HIV infection and a history of AIDS-defining opportunistic infections

Sponsors & Collaborators

• Mohammed Milhem: lead
• University of Iowa: collaborator

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma

Interventions

Selenomethionine; Axitinib; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Organoselenium Compounds; Organic Chemicals; Methionine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mohammed Milhem, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 6, 2022
• Study Start: September 19, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)