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Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05363631
Recruitment Status : Recruiting
First Posted : May 6, 2022
Last Update Posted : September 21, 2022
Sponsor:
Collaborator:
University of Iowa
Information provided by (Responsible Party):
Yousef Zakharia, University of Iowa

Study Description
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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).

Condition or disease Intervention/treatment Phase
Clear Cell Renal Cell Carcinoma Clear Cell Renal Cell Carcinoma Metastatic Drug: Selenomethionine (SLM) Drug: Axitinib Drug: Pembrolizumab Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : September 19, 2022
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: 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)

Drug: Axitinib
Axitinib is a small molecule tyrosine kinase inhibitor.

Drug: Pembrolizumab
Pembrolizumab is a type of immunotherapy


Outcome Measures
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Primary Outcome Measures :
  1. Phase I - Dose limiting toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: From the initiation of treatment through three years ]
    To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients

  2. Phase II - Objective Response Rate (ORR) [ Time Frame: From the initiation of treatment through three years ]
    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


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: From the initiation of treatment through three years ]
    PFS will be defined as the time from treatment initiation to the date of first documentation of disease progression or death due to any cause

  2. Overall survival (OS) [ Time Frame: From the initiation of treatment through three years ]
    OS will be defined as the time from treatment initiation to the date of death due to any cause


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05363631


Contacts
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Contact: Yousef Zakharia, MD (319) 384-8076 yousef-zakharia@uiowa.edu
Contact: Janelle Born, RN (319) 356-4797 janelle-born@uiowa.edu

Locations
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United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Yousef Zakharia, MD    319-384-8076    yousef-zakharia@uiowa.edu   
Contact: Janelle Born, RN    (319) 356-4797    janelle-born@uiowa.edu   
Sponsors and Collaborators
Yousef Zakharia
University of Iowa
Investigators
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Principal Investigator: Yousef Zakharia, MD University of Iowa
More Information
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Responsible Party: Yousef Zakharia, Clinical Associate Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT05363631    
Other Study ID Numbers: 202104398
First Posted: May 6, 2022    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
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
Selenium
Pembrolizumab
Axitinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Antioxidants
Protective Agents
Physiological Effects of Drugs
Trace Elements
Micronutrients