Axitinib + Nivolumab for Kidney Cancer

Not currently recruiting at 300 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining axitinib and nivolumab for kidney cancer that cannot be surgically removed or has metastasized. Axitinib blocks certain enzymes to stop tumor growth, while nivolumab helps the immune system attack cancer cells. Researchers aim to determine if these treatments work better together than standard methods. This trial may suit individuals diagnosed with translocation renal cell carcinoma that is inoperable or metastatic. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both axitinib and nivolumab have been studied for their safety in treating kidney cancer. For axitinib, about 20% of patients needed to lower their dose due to side effects, and about 8% stopped treatment completely. Common side effects included diarrhea and high blood pressure, yet most patients generally tolerate axitinib well.

Studies have found that nivolumab can cause serious side effects like diarrhea, fever, and lung inflammation, but these occurred in only about 2% of patients. Nivolumab has been used for some time in treating kidney cancer and has improved survival rates.

When used together, axitinib and nivolumab aim to combine their benefits. Although specific safety data for this combination is not detailed here, both drugs are known to have manageable side effects for most patients. This combination therapy is being explored to determine if it offers better results with acceptable safety levels. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they combine innovative approaches to tackle the disease. Axitinib works by inhibiting the growth of blood vessels that supply the tumor, while nivolumab boosts the immune system to better recognize and attack cancer cells. This combination therapy offers a dual-action approach that differs from traditional treatments like surgery or chemotherapy, potentially providing a more comprehensive defense against cancer progression. Additionally, the targeted nature of these treatments may lead to fewer side effects compared to conventional therapies.

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

Research shows that using axitinib and nivolumab together yields promising results for treating advanced kidney cancer. In this trial, participants may receive the combination of axitinib and nivolumab, axitinib alone, or nivolumab alone. Earlier studies demonstrated that the combination worked well for patients who hadn't been treated before. Axitinib alone has effectively shrunk tumors and helped patients live longer without disease progression. Nivolumab, a type of immunotherapy, has also lowered the risk of death and reduced tumor size in advanced kidney cancer. These findings suggest that axitinib and nivolumab could effectively treat a specific type of kidney cancer that is difficult to remove with surgery or has spread. ^{1 2 4 5 6}

Who Is on the Research Team?

James I Geller

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. 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 ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7265645/

Axitinib as a third or further line of treatment in renal cancer The majority of patients (13/68%) had clinical benefit from axitinib therapy resulting in 6 (27%) partial responses and 9 (41%) stabilizations of disease by ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.382

Real-world treatment outcomes in patients with advanced ... Axitinib with Pembrolizumab (AP) is one of the combinations which demonstrated improved outcomes in the KEYNOTE 426 study. We report real-world ...

5. 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 ...

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

Axitinib: A Review of its Safety and Efficacy in the ... Axitinib compared favorably, considering the risk of deterioration of symptoms, with functional assessment of cancer therapy—Kidney Cancer Symposium Index (FKSI ...