Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab

NCT ID: NCT05363631

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-19
• Study Completion Date: 2026-12-31

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).

Detailed Description

The proposed study is a single arm, open-label Phase I/II trial of Seleno-L Methionine (SLM) in sequential combination with the standard dose and schedule of Axitinib and Pembrolizumab in previously untreated patients with advanced ccRCC. The hypothesis is that adding SLM to the Pembrolizumab and Axitinib combination will improve efficacy without added toxicity.

This is a two-part study:

• Escalation Part 1: The study will begin with a dose-escalation study to find the maximum tolerated dose (MTD) of study drug, SLM.
• Expansion Part 2: Once the appropriate dose of SLM is determined, the second part of the study will begin.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Selenomethionine (SLM)

Intervention Type: 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)

Axitinib

Intervention Type: DRUG

Axitinib is a small molecule tyrosine kinase inhibitor.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is a type of immunotherapy

Interventions

Selenomethionine (SLM)

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)

Intervention Type: DRUG

Axitinib

Axitinib is a small molecule tyrosine kinase inhibitor.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is a type of immunotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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

No exclusions will be made based on sex, race, or ethnic background.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Iowa

OTHER

Sponsor Role: collaborator

Mohammed Milhem

OTHER

Sponsor Role: lead

Responsible Party

Mohammed Milhem

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mohammed Milhem, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Countries

United States

Other Identifiers

202104398

Identifier Type: -

Identifier Source: org_study_id