Cabozantinib for Kidney Cancer

Overseen By Ryan Romasko, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, Warfarin, Clopidogrel

Disqualifiers: Autoimmune disease, Uncontrolled hypertension, Cardiac arrhythmia, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 28-day cycles

111 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of cabozantinib (Cabometyx) alone or with nivolumab in treating certain advanced kidney cancers and neuroendocrine tumors. The aim is to determine if these treatments can manage cancer that has spread and has not been previously treated with cabozantinib. Suitable participants have advanced kidney cancer or neuroendocrine tumors that have recently worsened, without uncontrolled high blood pressure or recent major health issues such as a heart attack. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot use certain drugs that strongly affect liver enzymes (CYP3A4 inhibitors and inducers) and some blood thinners. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

A previous study found cabozantinib to be safe for patients with kidney cancer. Most patients tolerated it well, though some experienced side effects like tiredness and diarrhea. This treatment is already used for advanced kidney cancer, providing doctors with extensive knowledge of its effects.

Research has also shown that combining cabozantinib with nivolumab is safe for kidney cancer patients. Some experienced side effects such as diarrhea and fever, but proper care made these manageable. This combination is approved for advanced kidney cancer, further supporting its safety.

Overall, both treatments have a good safety record in kidney cancer. While side effects can occur, they are known and often manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cabozantinib for treating kidney cancer because it targets multiple pathways involved in tumor growth and metastasis, which is different from many current treatments that focus on single targets. This multi-targeted approach could potentially shut down cancer growth more effectively. When combined with nivolumab, an immune checkpoint inhibitor, cabozantinib may enhance the immune system's ability to attack cancer cells, offering a promising new strategy for fighting kidney cancer. Unlike standard treatments that might not offer such a combination of mechanisms, this dual approach could result in improved outcomes for patients.

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

Research has shown that cabozantinib may be promising for treating kidney cancer. In this trial, some participants will receive cabozantinib alone, which studies have shown results in a 34% reduction in disease progression or death, with 33% of patients experiencing tumor shrinkage. Another group will receive a combination of cabozantinib and nivolumab. Studies have demonstrated that this combination improves survival rates, reducing the risk of death by 40% compared to sunitinib. This combination has proven effective in advanced kidney cancer, offering long-term benefits. These results provide hope for better disease management for those considering this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Zibelman, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced kidney cancer, either untreated or not previously treated with Cabozantinib. They must be in fairly good health, understand the study and consent to it, agree to use contraception, and have at least one measurable tumor. Excluded are those with uncontrolled illnesses, certain heart conditions, other active cancers needing treatment, significant bleeding history or major surgery recently.

Inclusion Criteria

You have at least one clearly measurable tumor according to specific guidelines.

I have had multiple treatments for my condition.

I am either at low risk according to IMDC or cannot receive immunotherapy as my first treatment.

Exclusion Criteria

I have active brain or spinal cord cancer symptoms.

I am not using, nor do I need, drugs or foods that strongly affect drug metabolism.

I have issues with my digestive system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib with dose adjustments based on pre-specified criteria. Cohort B also receives monthly nivolumab infusions.

28-day cycles

Weekly follow-up for cycle 1, bi-weekly for cycle 2, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib

Trial Overview The trial is testing a different dosing schedule of Cabozantinib for patients with metastatic renal cell carcinoma (mRCC). It's open to all-risk frontline mRCC patients or any line mRCC patients who haven't tried Cabozantinib before.

How Is the Trial Designed?

Group I: Cabozantinib and nivolumab Experimental Treatment 2 Interventions

Cabozantinib treatment will receive monthly fix-dosed nivolumab infusions, and start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future.

Group II: Cabozantinib Experimental Treatment 1 Intervention

Cabozantinib treatment will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met the established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

Cabozantinib has been shown to significantly improve overall survival and progression-free survival in patients with advanced renal cell carcinoma compared to everolimus, as demonstrated in the METEOR trial.

While cabozantinib is effective, it is associated with several adverse events such as diarrhea, fatigue, and hypertension, which need to be managed carefully to ensure patient adherence and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma. Schmidinger, M., Danesi, R.[2022]

Cabozantinib (Cabometyx®) is now approved as a first-line treatment for advanced renal cell carcinoma (RCC) in treatment-naïve adults, expanding its use beyond patients who have already received VEGF-targeted therapy.

In a phase 2 trial, cabozantinib significantly improved median progression-free survival and objective response rates compared to the standard treatment sunitinib, while its side effects are manageable, similar to other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. Lyseng-Williamson, KA.[2020]

Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of the 25 heavily pretreated participants.

The treatment demonstrated a median progression-free survival of 12.9 months and a median overall survival of 15.0 months, with a safety profile consistent with other similar therapies, indicating its potential as a viable option for advanced RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Choueiri, TK., Pal, SK., McDermott, DF., et al.[2021]

Cabozantinib is an effective treatment for advanced hepatocellular carcinoma (HCC) after failure of sorafenib, showing significant improvement in overall survival and progression-free survival compared to placebo in the phase 3 CELESTIAL trial.

Common side effects of cabozantinib include palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea, which are important to manage in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. Trojan, J.[2021]

Cabozantinib significantly improves progression-free survival (PFS) and overall survival (OS) in patients with advanced renal cell carcinoma (RCC) who have previously undergone antiangiogenic therapy, as demonstrated in the METEOR trial.

The drug also shows a higher objective response rate compared to everolimus, while maintaining a manageable safety profile, making it a valuable treatment option for advanced RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Review in Advanced Renal Cell Carcinoma. Al-Salama, ZT., Keating, GM.[2018]

Cabozantinib has shown significant efficacy in treating advanced kidney cancer, with a 28% objective response rate and a median progression-free survival of 14.7 months based on a phase II trial involving patients with renal cancer.

The drug also demonstrated notable effectiveness in managing bone metastases, which is crucial for improving quality of life in patients, and further studies are planned to compare its effectiveness against standard VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as a novel therapy for renal cell carcinoma. Vaishampayan, U.[2022]

In a phase 3 trial involving 658 patients with metastatic renal-cell carcinoma, cabozantinib significantly improved progression-free survival (7.4 months) compared to everolimus (3.8 months), indicating its greater efficacy after VEGFR-targeted therapy.

Cabozantinib also showed a higher objective response rate (21% vs. 5% for everolimus) and a lower risk of progression or death (42% reduction), although both treatments had similar rates of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. Choueiri, TK., Escudier, B., Powles, T., et al.[2022]

In a study of 115 patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib, the drug showed a median progression-free survival of 12.5 months and a 12-month overall survival rate of 70.4%, indicating its efficacy in this population.

The safety profile of cabozantinib was acceptable, with only 4% of patients discontinuing treatment due to adverse events, and no treatment-related deaths reported, suggesting it is a tolerable option for patients with mRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Experience of Cabozantinib as Second- or Subsequent Line Treatment in Patients With Metastatic Renal Cell Carcinoma: Data From the Polish Managed Access Program. Bodnar, L., Kopczyńska, A., Żołnierek, J., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6854754/

Cabozantinib for Renal Cell Carcinoma A phase I study in patients with advanced RCC reported in 2014 showed a promising activity in heavily pretreated patients with a partial response rate of 28% [ ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0929664625001172

Real-world study of cabozantinib treatment of advanced ... The 5-year survival rate for metastatic kidney cancer is poor (15 % in 2021 in the USA) [1,6]. Cabozantinib is an oral inhibitor of multiple ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11332639/

The efficacy and safety of cabozantinib in patients ... The cabozantinib group showed a 34% reduction in disease progression or death and higher tumor response rates (33%) compared to the sunitinib ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1510016

Cabozantinib versus Everolimus in Advanced Renal-Cell ... The efficacy with cabozantinib was robust, with an estimated median progression-free survival of 7.4 months, as compared with 3.8 months with ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.316

Association of cabozantinib dose reductions for toxicity with ... We compared outcomes by dose reduction status, including objective response rate (ORR), time to treatment failure (TTF), and overall survival ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5905684/

Management of Adverse Events Associated with ... This review reports on the safety profile of cabozantinib in patients with advanced renal cell carcinoma and offers guidance on the management of adverse ...

7. cabometyx.com cabometyx.com/kidney-cancer/about-cabometyx

Learn about CABOMETYX in advanced kidney cancer See how CABOMETYX is used to treat a type of advanced kidney cancer known as advanced Renal Cell Carcinoma. See study results, side effects and important safety

8. sciencedirect.com sciencedirect.com/science/article/pii/S1558767323002173

Real-World Results of Cabozantinib Given as Alternative ... Cabozantinib is a widely used treatment strategy in metastatic renal cell carcinoma (mRCC), either in combination with the programmed cell death protein-1 (PD- ...

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2784989

Activity and Safety of Cabozantinib for Brain Metastases in ... These findings show considerable intracranial activity and an acceptable safety profile of cabozantinib in patients with renal cell carcinoma and brain ...

10. cabometyx.com cabometyx.com/kidney-cancer

Advanced Kidney Cancer Treatment Option| CABOMETYX ... CABOMETYX is used to treat certain people with advanced kidney cancer (RCC) alone or in combination with OPDIVO. See indication and important safety ...