Cabozantinib vs Sunitinib for Kidney Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness and safety of two treatments, cabozantinib and sunitinib, for variant histology renal cell carcinoma (vhRCC), a type of advanced kidney cancer that has metastasized. Both treatments have approval for advanced kidney cancer, and the study aims to determine which is more effective for this condition. Individuals diagnosed with vhRCC who have either not received treatment or have undergone only one type of treatment without certain drugs may qualify for this study. Participants will receive treatment at MD Anderson Cancer Center. 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 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.

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

Previous studies found cabozantinib safe for treating kidney cancer. Patients experienced fewer severe side effects than expected, indicating it was generally well-tolerated for similar conditions. Another study confirmed its safety and effectiveness, even for patients with cancer that had spread to the brain.

Research on sunitinib showed it was safe for long-term use. Patients with advanced kidney cancer often tolerated it well for over two years. The side effects were manageable, and it effectively treated this type of cancer.

Both cabozantinib and sunitinib have FDA approval for advanced kidney cancer, indicating their safety for this use. These findings can offer reassurance about the treatments' safety for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle kidney cancer. Cabozantinib is unique because it targets multiple pathways involved in tumor growth, potentially inhibiting cancer spread more effectively than some current options. Sunitinib malate, on the other hand, is already a standard treatment, but its comparison to cabozantinib in this context could reveal important insights into which drug offers better outcomes. Both drugs are taken orally, providing a convenient treatment option for patients. These features make them promising candidates in the fight against kidney cancer.

What is the effectiveness track record for cabozantinib and sunitinib in treating kidney cancer?

This trial will compare cabozantinib and sunitinib for advanced kidney cancer. Research has shown that cabozantinib, which participants in one arm of this trial may receive, can be effective for advanced kidney cancer. In one study, patients lived for an average of 7.4 months without their cancer worsening, and 28% of patients experienced some tumor shrinkage. Sunitinib, which participants in another arm of this trial may receive, is another proven treatment for advanced kidney cancer. In one trial, patients lived for an average of 6.0 months without their cancer worsening and had an overall survival of 24.7 months. While both medications are used for advanced kidney cancer, cabozantinib might help some patients go longer without disease progression. ^{2 6 7 8 9}

Who Is on the Research Team?

Matthew Campbell, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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. clinical-genitourinary-cancer.com clinical-genitourinary-cancer.com/article/S1558-7673(23)00217-3/fulltext

Real-World Results of Cabozantinib Given as Alternative ... The aim of this retrospective study was to analyze the pattern of cabozantinib treatment and its efficacy in a real-world cohort of patients ...

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/PMC11332639/

The efficacy and safety of cabozantinib in patients ... Positive results were observed for cabozantinib, with a 40% reduction in disease progression or death and a 23% tumor response rate compared to ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16538

Cabozantinib outcomes for metastatic renal cell carcinoma ... Conclusions: Overall, Cabozantinib showed better than expected response rates, and the toxicities in our NHS tertiary hospital were less severe ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37926597/

Real-World Results of Cabozantinib Given as Alternative ... By IMDC criteria, 32.4%, 59.2%, and 8.5% were classified as favorable, intermediate and poor risk respectively. Cabozantinib was offered as a 2nd-line or 3rd- ...

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 ...