Cabozantinib vs Sunitinib for Kidney Cancer

Recruiting at 2 trial locations

Overseen By Matthew Campbell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, 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

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks per cycle

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to compare the safety and effectiveness of cabozantinib and sunitinib when given to patients with metastatic (has spread) variant histology renal cell carcinoma (vhRCC), a type of kidney cancer. This is an investigational study. Cabozantinib and sunitinib are both FDA approved and commercially available for the treatment of advanced kidney cancer, including vhRCC. The study doctor can explain how the study drugs are designed to work. Up to 84 participants will be enrolled in this study. All will take part at MD Anderson.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like strong CYP3A4 inducers or certain anticoagulants. It's best to discuss your current medications with the study doctor.

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

Cabozantinib has shown promising results in treating kidney cancer, with a 28% response rate and stable disease in 62% of patients, along with a median progression-free survival of 14.7 months. It is particularly effective for patients with bone metastases, which are often linked to worse outcomes. ^{1 2 3 4 5}

What safety information is available for Cabozantinib and Sunitinib in treating kidney cancer?

Both Cabozantinib and Sunitinib have been studied for safety in treating kidney cancer. Common serious side effects for Cabozantinib include diarrhea, fatigue, and high blood pressure, while Sunitinib can cause fatigue, diarrhea, skin rash, and high blood pressure. Both drugs have a high rate of serious side effects, but these are common in cancer treatments. ^{2 4 6 7 8}

How does the drug Cabozantinib differ from other treatments for kidney cancer?

Cabozantinib is unique because it targets multiple tyrosine kinases (proteins involved in cancer growth) and has shown better results than sunitinib in prolonging progression-free survival in advanced kidney cancer. It is also effective in treating bone metastases, which are often associated with worse outcomes in kidney cancer patients. ^{1 2 9 10 11}

Research Team

Matthew Campbell, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with a specific type of kidney cancer that has spread and may have had one prior treatment excluding certain drugs. They should be in good physical condition, not pregnant, able to follow the study plan, and willing to use contraception. People with certain medical conditions or who've taken specific treatments recently can't join.

Inclusion Criteria

I understand the study requirements and have signed the consent form.

You have had a recent assessment of all known disease sites using scans like CT, MRI, or bone scan within the last 28 days before starting the medication.

Before starting the medication, your blood and organ function need to be within certain levels. For example, your white blood cell count needs to be at least 2500/mm^3, and your bilirubin levels need to be below a certain number.

Exclusion Criteria

My kidney cancer is a specific type without any clear cell components.

I am on certain blood thinners or platelet inhibitors, but not for brain metastases.

I have fully healed from any major surgery 1 month before starting the treatment and have no ongoing complications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either cabozantinib or sunitinib. Cabozantinib is taken daily, while sunitinib follows a 4 weeks on/2 weeks off schedule.

6 weeks per cycle

Visits every 6 weeks for physical exams, EKGs, and blood tests

End-of-Treatment

About 30 days after the last dose, participants undergo a physical exam, EKG, and blood tests.

4 weeks

1 visit (in-person)

Long-Term Follow-up

Participants have imaging scans every 6 weeks for the first year, then every 6 months. Follow-up calls or record reviews occur every 3 months.

Up to 2 years

Treatment Details

Interventions

• Cabozantinib
• Sunitinib Malate

Trial Overview The trial aims to compare the safety and effectiveness of two FDA-approved drugs for advanced kidney cancer: cabozantinib and sunitinib malate. Participants will receive either drug to determine which works better against this particular form of cancer.

Participant Groups

Group I: Group 2 (sunitinib malate) Experimental Treatment 1 Intervention

Participants receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Group 1 (cabozantinib) Experimental Treatment 1 Intervention

Participants receive cabozantinib PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

Findings from Research

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]

Sunitinib is an effective treatment for advanced metastatic renal cell carcinoma (mRCC), showing a significant improvement in progression-free survival compared to interferon-alpha, with 11 months for sunitinib versus 5 months for interferon-alpha in a Phase III study.

In Phase II trials, sunitinib demonstrated a partial response rate of 40% and 34% as a second-line therapy for mRCC patients who did not respond to previous cytokine treatments, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. Chouhan, JD., Zamarripa, DE., Lai, PH., et al.[2018]

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]

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]

In a study of 41 patients with advanced renal cell carcinoma and renal impairment, both sunitinib and sorafenib showed similar efficacy in terms of progression-free survival (6.6 months for sunitinib vs 5.8 months for sorafenib) and overall survival (65.9 months vs 58.0 months).

However, sunitinib was associated with a higher frequency of grade 3 or higher adverse events compared to sorafenib, indicating a need for careful monitoring of side effects, especially in patients with prior kidney surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. Takayama, T., Kubo, T., Yamazaki, M., et al.[2020]

In a Phase III trial involving treatment-naive patients with metastatic renal cell carcinoma (mRCC), sunitinib significantly improved progression-free survival compared to IFN-α, demonstrating its efficacy as a first-line treatment.

Sunitinib is effective even in challenging cases, such as patients with non-clear cell histology or those who are refractory to other treatments, and while it has common side effects like fatigue and hypertension, these may also indicate better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of sunitinib in renal cell carcinoma: where are we now? Czarnecka, AM., Szczylik, C., Rini, B.[2018]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. [2018]

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

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. [2022]

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

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Sorafenib and sunitinib for elderly patients with renal cell carcinoma. [2018]

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

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. [2020]

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

Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. [2022]

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

The use of sunitinib in renal cell carcinoma: where are we now? [2018]

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

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

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

Quality-adjusted survival with first-line cabozantinib or sunitinib for advanced renal cell carcinoma in the CABOSUN randomized clinical trial (Alliance). [2022]

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

Mixed Results for Sunitinib in Renal Cancer. [2018]