Axitinib + Nivolumab for Kidney Cancer

Recruiting at 291 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antidepressants, Immunosuppressants

Disqualifiers: Transplant history, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 31

Duration: 2 years

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well axitinib and nivolumab work in treating patients with TFE/translocation renal cell carcinoma that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving axitinib and nivolumab may work better in treating patients with TFE/translocation renal cell carcinoma compared to standard treatment, including surgery, chemotherapy, or immunotherapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take medications that affect the metabolism of nivolumab and/or axitinib within 7 days before starting the trial. It's best to discuss your current medications with the trial team.

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

Research shows that similar drug combinations, like Axitinib with Pembrolizumab, have a high response rate in advanced kidney cancer, suggesting that combining Axitinib with immune checkpoint inhibitors can be effective. Additionally, Axitinib and Nivolumab have been used as second-line treatments for kidney cancer, indicating their potential effectiveness. ^{1 2 3 4 5}

Is the combination of Axitinib and Nivolumab safe for treating kidney cancer?

Axitinib, when combined with immune checkpoint inhibitors like Nivolumab, has been studied for safety in treating kidney cancer. Common side effects include diarrhea, fatigue, and high blood pressure, but these are generally manageable with proper monitoring and care. ^{1 6 7 8 9}

How is the drug combination of Axitinib and Nivolumab unique for treating kidney cancer?

The combination of Axitinib and Nivolumab is unique because it combines a targeted therapy (Axitinib) that blocks specific proteins involved in cancer growth with an immune checkpoint inhibitor (Nivolumab) that helps the immune system attack cancer cells. This dual approach is part of a new standard of care for advanced kidney cancer, offering a different mechanism of action compared to traditional treatments. ^{1 10 11 12 13}

Research Team

James I Geller

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients with a specific kidney cancer called TFE/translocation renal cell carcinoma that can't be surgically removed or has spread. Participants must meet various health criteria, including proper organ function and blood counts, and not have received certain treatments recently. It's open to individuals as young as one year old who are expected to live at least 8 weeks.

Inclusion Criteria

My liver function tests are within normal limits.

My blood clotting time is normal or managed with medication.

I've been on stable blood pressure medication for over a week.

Exclusion Criteria

I have been treated with more than one anti-VEGF medication.

I have not had a stem cell or solid organ transplant.

I haven't had cancer treatment with monoclonal antibodies in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axitinib and/or nivolumab for up to 26 cycles (2 years) depending on the assigned arm

2 years

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, then at physician's discretion

Treatment Details

Interventions

• Axitinib
• Nivolumab

Trial Overview The study tests axitinib and nivolumab in treating unresectable or metastatic tRCC. Axitinib blocks enzymes needed for tumor growth, while nivolumab, an immunotherapy drug, helps the immune system attack cancer cells. The goal is to see if this combination works better than standard treatments.

Participant Groups

Group I: Arm C (nivolumab) Experimental Treatment 1 Intervention

Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (axitinib) Experimental Treatment 1 Intervention

Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C)

Group III: Arm A (axitinib, nivolumab) Experimental Treatment 2 Interventions

Patients receive axitinib PO BID on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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]

Combination therapies using immune checkpoint inhibitors, such as axitinib plus pembrolizumab, have shown improved outcomes compared to traditional sequential monotherapy in patients with metastatic renal cell carcinoma.

Phase III trials indicate that these combination regimens significantly enhance both progression-free survival and overall survival, addressing the issue of drug resistance seen with single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. Spisarová, M., Melichar, B., Vitásková, D., et al.[2021]

The combination of avelumab and axitinib showed promising antitumor activity in treatment-naive patients with advanced renal-cell carcinoma, with 58% of patients achieving confirmed objective responses in the study involving 55 participants.

The safety profile of the combination treatment was manageable, with adverse events similar to those seen with each drug alone, and the maximum tolerated dose was established as avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Choueiri, TK., Larkin, J., Oya, M., et al.[2022]

Axitinib combined with immune checkpoint inhibitors (ICI) like pembrolizumab or avelumab is now approved for treating advanced renal cell carcinoma, but distinguishing between adverse events (AEs) caused by each treatment is crucial for optimizing therapy.

Experts identified specific AEs such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues that require unique management strategies when using axitinib-ICI combinations, emphasizing the need for careful clinical monitoring and tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Grünwald, V., Voss, MH., Rini, BI., et al.[2021]

Nivolumab-ipilimumab is the most cost-effective first-line treatment for metastatic clear-cell renal cell carcinoma (mRCC), with an incremental cost-effectiveness ratio (ICER) of $34,190 per quality-adjusted life year (QALY) compared to sunitinib.

In contrast, pembrolizumab-axitinib was found to be not cost-effective, with an ICER of $12,630,828 per QALY, and resulted in shorter QALY gains (1.99) compared to nivolumab-ipilimumab (3.23 QALY).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma. Chan, A., Dang, C., Wisniewski, J., et al.[2023]

The combination of avelumab and axitinib has shown superior response rates and progression-free survival in treatment-naïve patients with metastatic renal cell carcinoma compared to sunitinib, based on the Javelin 101 phase III trial.

Despite the improved response rates, there was no significant difference in overall survival after 11.6 months of follow-up, and the safety profile of avelumab/axitinib was found to be tolerable with manageable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy. Leslie, I., Boos, LA., Larkin, J., et al.[2021]

Axitinib is an effective second-line treatment for advanced renal cell carcinoma (RCC), showing significantly prolonged median progression-free survival compared to sorafenib in the phase III AXIS trial.

The tolerability profile of axitinib is manageable, with common side effects including diarrhea, hypertension, and fatigue, making it a viable option for patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. Keating, GM.[2018]

Recent randomized trials have shown that the combination of pembrolizumab and axitinib significantly improves survival in patients with metastatic clear-cell renal cell carcinoma, establishing it as a new standard of care.

This treatment is recommended for all treatment-naïve patients, regardless of their risk group, according to updated guidelines from the European Association of Urology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. Albiges, L., Powles, T., Staehler, M., et al.[2020]

The combination of ipilimumab and nivolumab is considered a feasible first-line treatment for metastatic renal cell carcinoma, showing an acceptable safety profile compared to sunitinib monotherapy, based on a systematic review and meta-analysis of four randomized controlled trials.

Different immune-based combinations, including nivolumab plus ipilimumab and pembrolizumab plus axitinib, exhibit varying toxicity profiles, highlighting the importance of personalized treatment choices and the need for improved management of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Massari, F., Mollica, V., Rizzo, A., et al.[2022]

References

1. 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]

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

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

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

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Clinical outcomes of second-line treatment following prior targeted therapy in patients with metastatic renal cell carcinoma: a comparison of axitinib and nivolumab. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]

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

A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma. [2023]

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

Axitinib for the treatment of metastatic renal cell carcinoma: recommendations for therapy management to optimize outcomes. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. [2018]

11. Australia pubmed.ncbi.nlm.nih.gov

A comparative study on nivolumab and axitinib as secondary treatment in patients with metastatic renal cell carcinoma: A multi-institutional retrospective study in Japan. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. [2022]