Combining Seleno-L Methionine with Axitinib and Pembrolizumab for Kidney Cancer

Phase I/II Study of Seleno-L Methionine (SLM) in Sequential Combination With Fixed Doses and Schedules of Axitinib and Pembrolizumab (SAP) in Locally Advanced and Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)

This study is testing if adding a new supplement called Seleno-L Methionine to standard kidney cancer treatments can help patients with advanced clear cell renal cell carcinoma feel better without causing more side effects.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Iowa (Academic / other)
• Drugs / interventions: immunotherapy, Pembrolizumab, Axitinib
• Locations: 1 site (Iowa City, Iowa)
• Trial ID: NCT05363631 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of Seleno-L Methionine (SLM) when used alongside standard treatments Axitinib and Pembrolizumab in patients with advanced clear cell renal cell carcinoma (ccRCC). It is a single-arm, open-label Phase I/II study that will first determine the maximum tolerated dose of SLM before expanding to assess its efficacy. The hypothesis is that the addition of SLM will enhance treatment effectiveness without increasing toxicity for patients who have not previously received treatment for their metastatic disease.

Who should consider this trial

Good fit: Ideal candidates for this study are adults over 18 with locally advanced or metastatic clear cell renal cell carcinoma who have not received prior treatment.

Not a fit: Patients with non-clear cell renal cell carcinoma or those who have previously undergone treatment for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with advanced kidney cancer.

How similar studies have performed: While the combination of Axitinib and Pembrolizumab has been studied, the addition of Seleno-L Methionine is a novel approach that has not been extensively tested.

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.

Where this trial is running

Iowa City, Iowa

• University of Iowa Hospitals & Clinics — Iowa City, Iowa, United States (Recruiting)

Study contacts

• Principal investigator: Bilal Rahim, MD — University of Iowa
• Study coordinator: Bilal Rahim, MD

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