Cabozantinib for Prostate Cancer

Recruiting at 5 trial locations

Overseen By Elisabeth Heath, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: LHRH analogues

Must not be taking: Kinase inhibitors, Abiraterone, Enzalutamide

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

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

Compensation: Varies

Number of Visits: 12

Duration: Approximately 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the effects of cabozantinib (Cabometyx) on patients with metastatic castrate-resistant prostate cancer (mCRPC), a cancer type that grows despite low testosterone levels. Researchers believe cabozantinib may shrink tumors in patients with specific genetic markers or liver metastases. The trial seeks men with a confirmed diagnosis of prostate cancer that has spread, particularly to the liver, who are willing to undergo tumor biopsies. As a Phase 2 trial, this research measures cabozantinib's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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

The trial protocol does not specify if you need to stop all current medications, but you cannot have taken certain cancer treatments like abiraterone acetate or enzalutamide within 2 weeks before starting the trial. You must also avoid certain anticoagulants like warfarin, but low-dose aspirin and some other anticoagulants are allowed.

Is there any evidence suggesting that cabozantinib is likely to be safe for humans?

Research has shown that cabozantinib has been tested with other drugs to treat advanced prostate cancer. Some studies found that combining cabozantinib with atezolizumab can help patients live longer without their cancer worsening, indicating the drug's effectiveness against cancer.

Regarding safety, cabozantinib has been used in other medical studies and is known to cause side effects such as tiredness, diarrhea, and high blood pressure. These side effects were reported when cabozantinib was combined with other treatments, so they might not all occur when cabozantinib is used alone.

Since this trial is in the early testing stages, researchers are still learning about how well people tolerate cabozantinib. They are gathering information to understand its safety and potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard treatments for prostate cancer, such as hormone therapy, surgery, and radiation, Cabozantinib works differently by targeting specific proteins that help cancer cells grow and spread. This unique mechanism of action focuses on inhibiting the activity of tyrosine kinases, which are involved in tumor growth and angiogenesis. Researchers are excited about Cabozantinib because it has the potential to effectively slow the progression of prostate cancer by cutting off the blood supply to the tumor, offering a promising option for patients who may not respond well to traditional therapies.

What evidence suggests that cabozantinib might be an effective treatment for prostate cancer?

Research has shown that cabozantinib, which participants in this trial will receive, may help treat advanced prostate cancer. In some studies, it caused tumors to shrink in patients with various types of cancer, including prostate cancer. Notably, cabozantinib improved bone scans in men with advanced prostate cancer, suggesting potential benefits for cancer that has spread to the bones. Additionally, when combined with another drug, cabozantinib reduced the risk of disease progression or death by 35% in patients with prostate cancer that has spread and does not respond to standard hormone treatments. These findings suggest that cabozantinib could effectively manage advanced prostate cancer resistant to usual therapies. ^{1 3 6 7 8}

Who Is on the Research Team?

David M Nanus, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic castrate resistant prostate cancer (mCRPC) that's progressing. They must have a certain level of organ function, agree to biopsies, and not have had specific treatments recently. Participants need evidence of gene changes targeted by cabozantinib and must use contraception if fertile.

Inclusion Criteria

Capable of understanding and complying with the protocol requirements and must have signed the informed consent document

My organs and bone marrow are working well.

I am older than 18 years.

Exclusion Criteria

I haven't taken any small molecule kinase inhibitors in the last 2 weeks.

I do not have any major ongoing health issues like heart or stomach problems, or serious bleeding.

My heart's electrical activity (QTcF) is not over 500 ms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabozantinib continuously until radiographic progression or discontinuation due to toxicity

Approximately 12 months

Routine SOC visits including medical history, vitals, blood collection, imaging, EKG, and tumor biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 12 weeks

Up to 2 years

In-clinic or telephone contact every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib

Trial Overview The study tests the effects of cabozantinib on mCRPC patients selected based on molecular criteria like gene amplification or mutations. It aims to see if this drug can shrink tumors or slow their growth in these specifically chosen patients.

How Is the Trial Designed?

Group I: Cabozantinib Arm Experimental Treatment 1 Intervention

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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

In a phase II trial involving 171 men with castration-resistant prostate cancer (CRPC), cabozantinib demonstrated significant clinical activity, with 72% of patients showing regression in soft tissue lesions and 68% showing improvement in bone scans.

Cabozantinib significantly improved progression-free survival (PFS) compared to placebo, with a median PFS of 23.9 weeks versus 5.9 weeks, and also led to reductions in bone pain and narcotic use in many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary on "Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial." Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, SchoffskiSchöffski P, Scheffold C, Weitzman AL, Hussain M, University of Michigan, Ann Arbor, MI. J Clin Oncol 2013;31(4):412-9. doi: 10.1200/JCO.2012.45.0494. Epub 2012 Nov 19. Trump, DL.[2018]

In a study of 81 patients with metastatic castration-resistant prostate cancer receiving cabozantinib, 81% showed a positive response in bone scans, but only 18% had a response in soft tissue, indicating that cabozantinib is more effective for bone metastases than soft tissue lesions.

Despite no significant associations found between plasma biomarkers and treatment response, several biomarkers showed notable changes during treatment, suggesting that cabozantinib affects the tumor microenvironment and may inform future combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial. Leibowitz-Amit, R., Pintilie, M., Khoja, L., et al.[2018]

Cabozantinib, a multitargeted tyrosine kinase inhibitor, shows promise in improving bone scans, bone turnover markers, and pain response in men with castration-resistant prostate cancer (CRPC), indicating its efficacy in managing bone metastases.

Despite its effectiveness, cabozantinib is associated with significant adverse events that can lead to dose reductions and treatment discontinuation; however, lower doses maintain high activity with reduced toxicity, suggesting a potential for safer administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting MET and vascular endothelial growth factor receptor signaling in castration-resistant prostate cancer. Lee, RJ., Smith, MR.[2023]

In a study of 62 patients with hormone-naïve metastatic prostate cancer, cabozantinib combined with androgen deprivation therapy (ADT) showed a median progression-free survival (mPFS) of 16.1 months, indicating promising efficacy in delaying disease progression.

The treatment resulted in significant reductions in prostate-specific antigen (PSA) and other biomarkers in a high percentage of patients, although 85% experienced dose reductions due to adverse events, primarily hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer. Corn, PG., Zhang, M., Nogueras-Gonzalez, GM., et al.[2023]

In a phase II study involving 144 patients with castration-resistant prostate cancer, cabozantinib demonstrated significant efficacy, with 63% of patients showing a bone scan response and 57% experiencing meaningful pain relief.

Cabozantinib was associated with improvements in various clinical outcomes, including reductions in narcotic use and measurable soft tissue disease, while the most common severe side effects were fatigue and hypertension, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. Smith, MR., Sweeney, CJ., Corn, PG., et al.[2021]

In a phase II trial involving 171 men with castration-resistant prostate cancer (CRPC), cabozantinib demonstrated significant clinical activity, with 72% of patients showing regression in soft tissue lesions and 68% showing improvement in bone scans.

Cabozantinib significantly improved progression-free survival (PFS) compared to placebo, with a median PFS of 23.9 weeks versus 5.9 weeks, and also led to reductions in bone pain and narcotic use in many patients, although some experienced grade 3 adverse events like fatigue and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. Smith, DC., Smith, MR., Sweeney, C., et al.[2022]

Cabozantinib, which inhibits MET and VEGFR2 signaling, has shown clinical benefits in early trials for men with metastatic prostate cancer, indicating its potential as an effective treatment option.

Preclinical studies suggest that cabozantinib not only targets cancer cells directly but also disrupts the supportive environment (angiogenesis and stromal cells) that allows metastasis to thrive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib and prostate cancer: inhibiting seed and disrupting soil? Lee, RJ., Smith, MR.[2021]

In a study of 25 men with metastatic castration-resistant prostate cancer (mCRPC), cabozantinib demonstrated significant efficacy, with 77% of patients achieving stable disease or better after 12 weeks, and a median progression-free survival of 43.7 weeks.

Cabozantinib led to notable changes in bone scans for 36% of patients, indicating its potential to improve bone health in mCRPC, alongside changes in biomarkers related to bone formation and the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Smith, DC., Daignault-Newton, S., Grivas, P., et al.[2022]

Recent advancements in treating castration-resistant prostate carcinoma include the approval of four new agents—abiraterone, cabazitaxel, enzalutamide, and radium-223 dichloride—that have been shown to improve overall survival for patients.

Cabozantinib, a targeted therapy that inhibits MET and VEGFR-2, has demonstrated promising results in clinical trials and may become a key treatment option for this type of prostate cancer, although further research is needed to determine its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma. Pinto, A.[2014]

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]

Citations

1. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00209-8/abstract

Cabozantinib plus atezolizumab in metastatic prostate ... After a median follow-up of 11·8 months (IQR 9·9–19·3), cabozantinib plus atezolizumab significantly improved progression-free survival versus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110249/

Cabozantinib in Patients With Advanced Prostate Cancer In phase I clinical studies, treatment with cabozantinib resulted in tumor regression in multiple cancer types. On the basis of the broad activity, a phase II ...

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-detailed-results-phase-3-contact-02-pivotal

Exelixis Announces Detailed Results of Phase 3 CONTACT ... Cabozantinib in combination with atezolizumab reduced the risk of disease progression or death by 35% in patients with metastatic castration-resistant prostate ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8802308/

Efficacy and Effect of Cabozantinib on Bone Metastases in ... Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04631744

Study Details | NCT04631744 | Cabozantinib in Patients ... The purpose of this study is to determine what effects (good and bad) cabozantinib has in treatment of patients with metastatic castrate resistant prostate ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40523369/

final analyses from a phase 3, open-label, randomised trial After a median follow-up of 11·8 months (IQR 9·9-19·3), cabozantinib plus atezolizumab significantly improved progression-free survival versus ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.186

A phase 1b study of cabozantinib and nivolumab with ... Conclusions: Here, we present updated clinical and immune correlative findings of the first trial of cabozantinib in combination with nivolumab ...

8. ipsen.com ipsen.com/press-releases/latest-phase-iii-trial-data-investigating-cabometyx-in-combination-with-immunotherapy-to-be-presented-at-asco-gu-2024/

Latest Phase III trial data investigating Cabometyx® in ... Detailed top-line results from Phase III CONTACT-02 trial demonstrated statistically significant progression-free survival benefit for ...