33 Participants Needed

Cabozantinib + Atezolizumab for Prostate Cancer

SS
Overseen BySusan Sharry
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether cabozantinib and atezolizumab work to shrink tumors in patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and atezolizumab may kill more tumor cells in patients with metastatic castrate-resistant prostate cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like chemotherapy, immunotherapy, or kinase inhibitors shortly before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that Cabozantinib, when combined with Atezolizumab, has shown promising results in treating metastatic castration-resistant prostate cancer, especially in patients who have limited options after other hormone therapies. Cabozantinib is known to enhance the immune response, which may improve the effectiveness of Atezolizumab, an immune checkpoint inhibitor.12345

Is the combination of Cabozantinib and Atezolizumab generally safe for humans?

Atezolizumab has been used in various cancer treatments and is generally considered to have a manageable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation, liver inflammation, and thyroid issues. The safety of Cabozantinib in combination with Atezolizumab specifically for prostate cancer may not be fully established, but both drugs have been used safely in other cancer treatments.678910

How is the drug combination of Cabozantinib and Atezolizumab unique for treating prostate cancer?

The combination of Cabozantinib and Atezolizumab is unique because Cabozantinib, a drug that blocks certain proteins involved in cancer growth, works with Atezolizumab, an immune system booster, to potentially enhance the body's ability to fight prostate cancer. This approach is being tested for patients with advanced prostate cancer who have limited treatment options after other therapies.123411

Research Team

Umang Swami | University of Utah Health

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

Men aged 18+ with metastatic castration-resistant prostate cancer that has spread and progressed despite hormone therapy. They must have certain blood, liver, and kidney function levels, agree to contraception use, not have had certain recent treatments or other cancers within 3 years, no severe illnesses or infections, and be able to follow the study plan.

Inclusion Criteria

Serum albumin >= 2.5 g/dl
Lymphocyte count >= 0.5 x 10^9/L (500/uL)
Alkaline phosphatase (ALP) =< 3 × institutional ULN
See 23 more

Exclusion Criteria

My cancer has spread, but I don't have pain or loss of function from it.
I haven't had a live vaccine within 30 days before starting the study treatment.
I have brain metastases or cranial epidural disease.
See 28 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib orally once daily on days 1-21 and atezolizumab intravenously on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle, ongoing until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months until disease progression or start of another therapy.

Up to 3 years

Treatment Details

Interventions

  • Atezolizumab
  • Cabozantinib S-malate
Trial OverviewThe AtezoCab trial is testing if combining cabozantinib (a drug blocking enzymes for cell growth) with atezolizumab (an immunotherapy antibody) can shrink tumors in patients with advanced prostate cancer compared to current standard treatments.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (cabozantinib, atezolizumab)Experimental Treatment2 Interventions
Patients receive cabozantinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Atezolizumab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Tecentriq for:
  • Melanoma
  • Hepatocellular carcinoma
  • Small cell lung cancer
  • Non-small cell lung cancer
  • Urothelial carcinoma
🇪🇺
Approved in European Union as Tecentriq for:
  • Melanoma
  • Hepatocellular carcinoma
  • Small cell lung cancer
  • Non-small cell lung cancer
  • Urothelial carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials
1,169
Recruited
1,623,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study involving 132 patients with metastatic castration-resistant prostate cancer, the combination of cabozantinib and atezolizumab demonstrated an objective response rate of 23%, indicating promising antitumor activity after prior hormonal therapies.
While the treatment showed efficacy, 55% of patients experienced grade 3-4 treatment-related adverse events, with pulmonary embolism and diarrhea being the most common, suggesting that while the combination is effective, careful monitoring for side effects is necessary.
Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021).Agarwal, N., McGregor, B., Maughan, BL., et al.[2022]
Cabozantinib, which inhibits multiple receptor tyrosine kinases, is being evaluated in combination with the PD-L1 inhibitor atezolizumab for its potential to enhance treatment responses in men with metastatic castration-resistant prostate cancer (mCRPC).
A phase III trial (NCT04446117) is being designed to compare the efficacy of cabozantinib plus atezolizumab against a second novel hormone therapy in patients with mCRPC who have previously received hormone treatments, addressing a significant need for effective options in this patient population.
A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer.Agarwal, N., Azad, A., Carles, J., et al.[2022]
Cabozantinib, a multitarget tyrosine kinase inhibitor, is effective in treating medullary thyroid cancer, metastatic renal cell carcinoma, and hepatocellular carcinoma, and is now being tested in prostate cancer patients for its potential immunostimulatory effects.
The drug induces immunogenic cell death in prostate cancer cells and alters dendritic cell behavior, suggesting it may enhance the effectiveness of immunotherapy by modifying the immune response against tumors.
Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib.Scirocchi, F., Napoletano, C., Pace, A., et al.[2021]

References

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). [2022]
A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. [2022]
Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib. [2021]
A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer. [2023]
Cabozantinib: a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma. [2014]
Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]
Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]
Atezolizumab: First Global Approval. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Cabozantinib and prostate cancer: inhibiting seed and disrupting soil? [2021]