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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine what effects (good and bad) cabozantinib has in treatment of patients with metastatic castrate resistant prostate cancer (mCRPC). The hypothesis for this trial is that cabozantinib has anti-tumor activity in a molecularly-selected group of patients with CRPC or patients with liver metastases.

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.

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

Cabozantinib has shown clinical benefits in early trials for men with metastatic prostate cancer, improving progression-free survival and showing activity in advanced cases, particularly in bone metastases. ^{1 2 3 4 5}

Is cabozantinib safe for humans?

Cabozantinib has been studied in various cancers, including prostate and liver cancer. Common serious side effects include hand-foot syndrome (skin reaction on palms and soles), high blood pressure, tiredness, and diarrhea. Lower doses may reduce these side effects while still being effective. ^{2 3 6 7 8}

How is the drug Cabozantinib unique for treating prostate cancer?

Cabozantinib is unique because it is an oral drug that targets specific proteins (MET and VEGFR2) involved in cancer growth and blood vessel formation, which helps to kill cancer cells and disrupt their supportive environment, especially in cases where the cancer has spread to the bones. ^{1 2 7 9 10}

Research Team

David M Nanus, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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]

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]

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 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]

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]

References

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

Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. [2022]

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

Cabozantinib and prostate cancer: inhibiting seed and disrupting soil? [2021]

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

A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2018]

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

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

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

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. [2021]

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

Targeting MET and vascular endothelial growth factor receptor signaling in castration-resistant prostate cancer. [2023]

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

Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. [2022]

10. United States 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. [2018]