SLM + Axitinib for Kidney Cancer

Overseen By Yousef Zakharia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mohammed Milhem

Must not be taking: CYP3A4 drugs

Disqualifiers: Pregnancy, Uncontrolled hypertension, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and understand the side effects of combining L-selenomethionine, a supplement that may inhibit tumor growth, with axitinib, a cancer drug. It targets advanced metastatic clear cell renal cell carcinoma, a challenging type of kidney cancer that has spread. Researchers hope this combination will surpass the effectiveness of current treatments. Patients with metastatic kidney cancer who have tried other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain drugs that affect liver enzymes, like some antibiotics and antifungals. There is a 2-week period required after your last systemic treatment before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of L-selenomethionine (SLM) and axitinib is generally well-tolerated by patients. In earlier studies, patients took up to 4000 micrograms of SLM with axitinib, and most managed it well. Common side effects included tiredness, diarrhea, high blood pressure, nausea, loss of appetite, cough, protein in the urine, and weight loss. These side effects are typical for cancer treatments and did not stop the study.

Axitinib is already used to treat advanced kidney cancer, and doctors are familiar with managing its side effects. Overall, the treatment with SLM and axitinib shows promising safety data, making it a potential option for those with advanced kidney cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Selenomethionine (SLM) and axitinib for kidney cancer because it introduces the use of SLM, an antioxidant amino acid that may help enhance the effects of axitinib. While axitinib is already a standard treatment targeting blood vessel growth in tumors, SLM could potentially improve its efficacy and reduce side effects by protecting healthy cells. This dual approach aims to not only inhibit tumor growth more effectively but also improve the overall treatment experience for patients.

What evidence suggests that this trial's treatments could be effective for advanced metastatic kidney cancer?

This trial will evaluate the combination of Selenomethionine (SLM) and Axitinib for treating advanced kidney cancer. Research suggests that L-selenomethionine (SLM) may inhibit tumor growth by preventing new blood vessel formation. In one study, patients taking a 4,000 microgram dose showed a 55.6% positive response, with effects lasting about 18.4 months. Axitinib has also demonstrated potential in treating various cancers, including kidney cancer. Specifically, in some studies, tumors shrank in about 70 out of 361 patients, with the disease remaining stable for an average of 12.4 months. Combining these treatments in this trial might offer a more effective approach to treating advanced kidney cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Mohammed Milhem, MBBS

Principal Investigator

University of Iowa Hospitals & Clinics

Are You a Good Fit for This Trial?

Adults with advanced metastatic clear cell renal cell carcinoma (CCRCC) who've had at least one systemic therapy can join this trial. They must have a target lesion, adequate organ function, and an ECOG status of 0-2. Pregnant women, recent major surgery patients, those with untreated brain metastases or uncontrolled hypertension are excluded.

Inclusion Criteria

Life expectancy of 12 weeks and more.

My liver tests are within the required range.

My kidney function, measured by creatinine levels, is within the normal range.

Exclusion Criteria

My blood pressure is over 150/90 mm Hg, even with medication.

I am not using and do not need drugs that affect liver enzymes.

I haven't had any other cancers in the last 5 years that could affect this treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Part 1

SLM will be given twice daily for 14 days followed by once daily dosing in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity.

14 days

Expansion Part 2

Patients will be treated at the maximum tolerated dose (MTD) of SLM determined in the Escalation Part 1. SLM will be given orally twice daily for 14 days, followed by once daily dosing in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity.

14 days

Pilot Phase

Dosing will begin at dose level 3 (4000, 5000, or 6000 mcg SLM calculated based on patients' BSA). SLM will be given orally twice daily for 14 days. Each cohort will enroll 2 evaluable patients.

14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Selenomethionine (SLM)

Trial Overview The trial is testing the safety and early effectiveness of combining axitinib with selenomethionine (SLM) in treating CCRCC. It includes dose escalation/expansion phases and a pilot study to determine effective selenium doses based on body surface area.

How Is the Trial Designed?

Group I: Study Treatment Experimental Treatment 2 Interventions

During the Dose-Escalation Part 1, patients will receive SLM twice daily for 14 days followed by SLM once daily in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity. During the Expansion Part 2, patients will be treated at the maximum tolerated dose (MTD) of SLM determined as 4000 mcg SLM. SLM will be given orally twice daily for 14 days followed by SLM once daily in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity. During the Pilot Phase, dosing will begin at dose level 3 (4000, 5000, or 6000 mcg SLM calculated based on patients' BSA). SLM will be given orally twice daily for 14 days. Each cohort will enroll 2 evaluable patients.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Mohammed Milhem

Lead Sponsor

Trials

9

Recruited

240+

Bilal G. Rahim

Lead Sponsor

Trials

2

Recruited

100+

Yousef Zakharia

Lead Sponsor

Trials

5

Recruited

160+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

In the phase III JAVELIN Renal 101 trial, avelumab plus axitinib demonstrated significantly improved progression-free survival (PFS) of 13.9 months compared to 8.5 months for sunitinib, indicating better efficacy in treating advanced renal cell carcinoma.

The overall survival (OS) trend also favored avelumab plus axitinib, with a hazard ratio of 0.79 compared to sunitinib, although the data is still immature and requires further follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. Haanen, JBAG., Larkin, J., Choueiri, TK., et al.[2023]

The ATLAS trial, involving 724 patients with locoregional renal cell carcinoma, found that axitinib did not significantly improve disease-free survival compared to placebo, leading to the trial's early termination due to futility.

However, in the highest-risk subgroup, axitinib showed a promising reduction in the risk of disease-free survival events, suggesting potential benefits for specific patients, despite similar rates of adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. Gross-Goupil, M., Kwon, TG., Eto, M., et al.[2023]

Axitinib demonstrated antitumor activity in patients with metastatic renal cell carcinoma (mRCC) who were refractory to prior therapies, achieving an objective response rate of 22.6% and a median duration of response of 17.5 months in a study of 62 patients.

The treatment was generally well-tolerated, with manageable mild to moderate adverse effects, including hand-foot syndrome and hypertension, indicating that axitinib could be a viable option for patients who have not responded to other VEGF-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. Rini, BI., Wilding, G., Hudes, G., et al.[2018]

The standard treatment for metastatic renal cell carcinoma involves using targeted therapies like VEGF inhibitors and mTOR inhibitors, emphasizing the importance of understanding their tolerability profiles to enhance patient adherence and clinical outcomes.

Effective management of adverse events (AEs) associated with these therapies is crucial, as it can significantly improve patients' quality of life during treatment, highlighting the important role of nurses in educating patients about AEs and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing patient adherence to targeted therapies in renal cell carcinoma. Creel, PA.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3825605/

Axitinib: A Review of its Safety and Efficacy in ... This agent has demonstrated promising activity in phase II trials for the treatment of various solid tumors in addition to RCC, including metastatic melanoma, ...

2. inlyta.com inlyta.com/axitinib/clinical-trial-results

INLYTA® (axitinib) Clinical Trial Results | Safety Info 70 of 361 patients taking INLYTA saw their tumors shrink compared to 34 of 362 patients taking Nexavar. This includes patients whose tumors shrank 30% or more ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36470258/

Real-World Study Evaluating Safety and Effectiveness of ... Axitinib dose reduction was required in 20% of the adverse events and discontinuation in 8%. Median progression-free survival was 12.4 months (95% confidence ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143923002867

Efficacy and safety of axitinib for metastatic renal cell ... The efficacy of axitnib is not affected by renal impairment. · Treatment outcomes including Objective response rate and Progression-free survival are were ...

5. actionkidneycancer.org actionkidneycancer.org/real-world-experience-with-axitinib-inlyta/

Real world experience with axitinib (Inlyta) The article suggests that the real world efficacy data for axitinib is similar to that seen in clinical trials, with a median overall survival of 16.4 months ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11961314/

Phase I Clinical Trial of High Doses of Seleno-L-methionine in ... SLM (4000 μg) in sequential combination with axitinib is well tolerated with encouraging efficacy. Introduction. There are approximately 82,000 new cases and ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.6_suppl.322

Phase I with expansion clinical trial of seleno-l-methionine ... The non-toxic SLM dose of 4000μg was administered orally twice daily (BID) for 14 days, followed by once daily in combination with axitinib 5 mg BID.

8. targetedonc.com targetedonc.com/view/promising-efficacy-and-safety-with-seleno-l-methionine-plus-axitinib-in-ccrcc

Promising Efficacy and Safety With Seleno-L-Methionine ... The most common AEs that patients experienced were fatigue, diarrhea, hypertension, nausea, anorexia, cough, proteinuria, and weight loss. The ...

9. inlyta.com inlyta.com/

INLYTA® (axitinib) Home Page | Safety Info INLYTA is a prescription medicine used to treat kidney cancer that has spread or cannot be removed by surgery (advanced renal cell carcinoma or RCC)

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.6_suppl.630

Phase1 clinical trial of high doses of Seleno-L-methionine ... Preliminary results of phase I clinical trial of high doses of seleno-L-methionine (SLM) in sequential combination with axitinib in previously ...