Chemoimmunotherapy for Prostate Cancer

(CHAMP Trial)

Recruiting at 1 trial location

Overseen By Julia Hurrelbrink, RN, BSN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Andrew J. Armstrong, MD

Must be taking: ADT

Must not be taking: Abiraterone, Enzalutamide, Anti-PD-1, others

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, 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

Compensation: Varies

Number of Visits: 10

Duration: 30 weeks

43 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of immune-boosting and chemotherapy drugs in men with aggressive prostate cancers. The treatment aims to strengthen the immune system to fight cancer and directly kill cancer cells.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain prostate cancer therapies or treatments like abiraterone, androgen receptor antagonists, or specific immunotherapies shortly before starting the trial.

What data supports the effectiveness of the drug combination used in the Chemoimmunotherapy for Prostate Cancer trial?

Research shows that cabazitaxel, a component of the treatment, has improved survival in men with advanced prostate cancer who have already received other treatments. Additionally, ipilimumab, another component, has shown activity in prostate cancer, especially in patients with lower disease burden. ^{1 2 3 4 5}

What safety data exists for chemoimmunotherapy treatments like Cabazitaxel and Ipilimumab in prostate cancer?

Cabazitaxel has been studied for safety in older patients with prostate cancer, showing some adverse drug reactions. Ipilimumab, used in prostate cancer, can cause immune-related side effects, but these are usually manageable with standard treatments. ^{2 6 7 8 9}

What makes the chemoimmunotherapy treatment for prostate cancer unique?

This treatment combines chemotherapy drugs (Cabazitaxel and Carboplatin) with immunotherapy drugs (Ipilimumab and Nivolumab), aiming to enhance the immune system's ability to fight cancer while also directly targeting cancer cells, which is a novel approach compared to standard treatments that typically focus on one method. ^{1 2 3 5 10}

Research Team

Andrew Armstrong, MD, ScM

Principal Investigator

Duke University

Eligibility Criteria

This trial is for men with advanced prostate cancer that has spread and shows neuroendocrine characteristics or aggressive behavior. Participants must have a good performance status, controlled testosterone levels through ongoing therapy, acceptable lab values, and be over 18 years old. They should not have psychiatric disorders affecting trial participation, recent other cancer treatments or live vaccines, active infections like HIV or hepatitis B/C, certain autoimmune diseases, severe neuropathy, untreated brain metastases or a history of specific prior treatments.

Inclusion Criteria

Life expectancy of over 3 months as determined by treating physician.

I am older than 18 years.

I agree to use effective birth control and not donate sperm while on cabazitaxel treatment.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I am currently being treated for an infection.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 10 cycles of nivolumab, ipilimumab, carboplatin, and cabazitaxel, followed by maintenance nivolumab and ipilimumab

30 weeks

10 cycles of 21 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Cabazitaxel
• Carboplatin
• Ipilimumab
• Nivolumab

Trial Overview The study tests the combination of nivolumab (an immunotherapy), ipilimumab (another immunotherapy), cabazitaxel (a chemotherapy drug), and carboplatin (a platinum-based chemo) in treating aggressive forms of prostate cancer. Up to 10 cycles will be given followed by maintenance doses until disease progression or unacceptable side effects occur. The study also looks at how these drugs affect the immune system and cancer biomarkers.

Participant Groups

Group I: Neuroendocrine Prostate Cancer (NEPC) or Aggressive Variant Prostate Cancer (AVPC) Experimental Treatment 4 Interventions

Subjects with neuroendocrine prostate cancer (NEPC) or aggressive variant prostate cancer (AVPC) will receive a combination of nivolumab, ipilimumab, carboplatin and cabazitaxel for up to 10 cycles of 21 days each. After carboplatin and cabazitaxel are discontinued, a combination of nivolumab and ipilimumab will be administered. Nivolumab will be administered intravenously at a dose of 360 mg every 3 weeks. Ipilimumab will be administered intravenously at a dose of 1 mg/kg every 6 weeks. Carboplatin will be administered intravenously at a dose of AUC 4 mg/ml per minute. Cabazitaxel will be administered intravenously at a dose of 20 or 25 mg/m2.

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

Andrew J. Armstrong, MD

Lead Sponsor

Trials

5

Recruited

150+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Adding carboplatin to cabazitaxel significantly improved progression-free survival in men with metastatic castration-resistant prostate cancer, increasing the median survival from 4.5 months to 7.3 months in a phase 2 trial with 160 participants.

While the combination treatment had more adverse events compared to cabazitaxel alone, it was still considered safe and well tolerated, with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. Corn, PG., Heath, EI., Zurita, A., et al.[2021]

Ipilimumab, a monoclonal antibody targeting CTLA-4, has shown potential activity in prostate cancer, particularly in patients with lower disease burden, despite not improving overall survival in a Phase III study.

While immune-related adverse events are common with ipilimumab treatment, they can generally be managed effectively using standard immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in the treatment of prostate cancer. Reese, Z., Straubhar, A., Pal, SK., et al.[2018]

Sipuleucel-T has shown to improve overall survival by 4 months in patients with castration-resistant prostate cancer, particularly benefiting those with favorable prognostic factors like minimal tumor burden and a Gleason score of ≤7.

New immunomodulatory treatments like ipilimumab and tasquinimod, along with antihormonal drugs such as abiraterone acetate, are emerging as promising options for managing castration-resistant prostate cancer, indicating a shift towards more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. Heidenreich, A.[2021]

Cabazitaxel is an effective second-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC), showing a median survival of 15.1 months compared to 12.7 months with mitoxantrone in a randomized trial.

While cabazitaxel has demonstrated efficacy, it is associated with significant adverse effects, including myelosuppression and febrile neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. Nightingale, G., Ryu, J.[2023]

Cabazitaxel, a new chemotherapy drug, has been shown to improve overall survival by 2.4 months in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment, compared to the older drug mitoxantrone.

While cabazitaxel is effective, it carries a risk of significant hematologic toxicity, including febrile neutropenia, necessitating the use of hematopoietic growth factors in cases of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. Lheureux, S., Joly, F.[2018]

In a study involving 112 patients with metastatic castration-resistant prostate cancer (mCRPC), cabazitaxel treatment showed a low incidence of serious side effects, such as neutropenic sepsis (6.3%) and severe diarrhea (4.5%), indicating a favorable safety profile.

Patients reported trends towards improved quality of life during treatment, suggesting that cabazitaxel may enhance overall well-being for those whose cancer progressed after docetaxel, although careful patient selection is necessary due to potential toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final quality of life and safety data for patients with metastatic castration-resistant prostate cancer treated with cabazitaxel in the UK Early Access Programme (EAP) (NCT01254279). Bahl, A., Masson, S., Malik, Z., et al.[2022]

Cabazitaxel is a potentially effective treatment for castration-resistant prostate cancer (CRPC) in patients aged 80 years and older, showing similar efficacy in overall survival and PSA response rates compared to younger patients.

The safety profile of cabazitaxel is comparable across age groups, with high rates of adverse drug reactions (ADRs) in both patients aged <80 (77.2%) and ≥80 years (79.6%), primarily involving hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. Matsubara, N., Suzuki, K., Kazama, H., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Ipilimumab, an anti-CTLA-4 monoclonal antibody, is a significant advancement in cancer immunotherapy, effectively targeting T-cell inhibitory checkpoints to enhance the immune response against tumors.

In a review of 44 prostate cancer patients treated with ipilimumab, it was found that while the therapy is effective, it is also associated with immune-related adverse events (irAEs) that require careful management with immunosuppressive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. Gao, J., He, Q., Subudhi, S., et al.[2022]

Immunotherapy is emerging as a promising fourth treatment option for castration-resistant prostate cancer (CRPC), alongside traditional therapies like surgery, radiation, and chemotherapy.

Current specific immunotherapies, such as Sipuleucel-T and anti-PD-1 monoclonal antibodies, show potential but have not yet achieved consistently satisfactory results, indicating that this field is still in development and may improve in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current status and prospects of immunotherapy for castration-resistant prostate cancer]. Yatsuda, J., Eto, M.[2014]

References

1. England pubmed.ncbi.nlm.nih.gov

Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. [2021]

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

Ipilimumab in the treatment of prostate cancer. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. [2021]

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

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. [2018]

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

Final quality of life and safety data for patients with metastatic castration-resistant prostate cancer treated with cabazitaxel in the UK Early Access Programme (EAP) (NCT01254279). [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. [2021]

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

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]

9. England pubmed.ncbi.nlm.nih.gov

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Current status and prospects of immunotherapy for castration-resistant prostate cancer]. [2014]