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

46 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Axitinib for kidney cancer?

Research shows that Axitinib, when used with another drug called pembrolizumab, has a 73% response rate in treating advanced kidney cancer. Additionally, Axitinib has been effective as a second-line therapy and as a first-line treatment for metastatic kidney cancer, indicating its potential benefit in treating this condition. ^{1 2 3 4 5}

Is the combination of Selenomethionine (SLM) and Axitinib safe for treating kidney cancer?

Axitinib, used for kidney cancer, can cause side effects like high blood pressure, liver and kidney issues, and heart problems. However, a study found that a selenium version of axitinib (Se-axitinib) reduced these side effects while still fighting kidney cancer effectively. This suggests that combining Selenomethionine with Axitinib might help reduce some of the treatment's side effects. ^{5 6 7 8 9}

What makes the drug SLM + Axitinib unique for kidney cancer treatment?

The combination of Selenomethionine (SLM) with Axitinib is unique because it aims to reduce the side effects commonly associated with Axitinib, such as high blood pressure and liver and kidney issues, while maintaining its effectiveness against kidney cancer. ^{1 7 10 11 12}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of L-selenomethionine when given together with axitinib in treating patients with clear cell renal cell carcinoma that has spread from the primary site (place where it started) to other places in the body and usually cannot be cured or controlled with treatment (advanced metastatic). L-selenomethionine may stop the growth of tumor cells by blocking the growth of new blood vessels necessary for tumor growth. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving L-selenomethionine together with axitinib may be a better treatment for advanced metastatic clear cell renal cell carcinoma.

Research Team

Mohammed Milhem, MBBS

Principal Investigator

University of Iowa Hospitals & Clinics

Eligibility Criteria

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

My liver tests are within the required 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Assessment of Efficacy, Safety, and Quality of Life of 124 Patients Treated With Axitinib as Second-Line Therapy for Metastatic Renal-Cell Carcinoma: Experience in Real-World Clinical Practice in Japan. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. [2023]

4. Australia pubmed.ncbi.nlm.nih.gov

The efficacy of axitinib as a first-line treatment for metastatic renal cell carcinoma. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Selenium substituted axitinib reduces axitinib side effects and maintains its anti-renal tumor activity. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Axitinib safety in metastatic renal cell carcinoma: suggestions for daily clinical practice based on case studies. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian "Real-World" SAX Study. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Current Landscape and the Potential Role of Hypoxia-Inducible Factors and Selenium in Clear Cell Renal Cell Carcinoma Treatment. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety With Axitinib in Previously Treated Patients With Metastatic Renal Cell Carcinoma. [2022]

12. England 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. [2023]