Chemoimmunotherapy for Prostate Cancer

(CHAMP Trial)

Not currently recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for men with neuroendocrine prostate cancer (NEPC) or aggressive prostate cancer variants. It combines four drugs: nivolumab and ipilimumab (immunotherapy drugs), and cabazitaxel and carboplatin (chemotherapy drugs), to evaluate their safety and effectiveness against these challenging cancer types. The trial also examines the drugs' effects on the body's immune system and specific cancer markers. Men whose prostate cancer has not responded to certain treatments and is progressing, with signs like spreading to other organs, might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

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.

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

Research is investigating the safety and effectiveness of a combination of four drugs—nivolumab, ipilimumab, cabazitaxel, and carboplatin—for treating aggressive prostate cancer. These drugs have been used separately in other treatments and have known side effects.

Nivolumab and ipilimumab, as immunotherapy drugs, can sometimes cause side effects like skin rashes or organ inflammation. Cabazitaxel and carboplatin, as chemotherapy drugs, may lead to side effects such as tiredness, low blood cell counts, or nausea.

This trial is in its early stages, focusing mainly on the safety of using these drugs together. Researchers are still gathering information on how well patients tolerate this combination.

For those considering joining the trial, it is important to know that side effects can vary among individuals. Participants will be closely monitored to help manage any side effects that occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this chemoimmunotherapy treatment for prostate cancer because it combines traditional chemotherapy with cutting-edge immunotherapy. While standard treatments often focus on hormone therapy or chemotherapy alone, this approach uses cabazitaxel and carboplatin to directly attack cancer cells and pairs them with nivolumab and ipilimumab, which help boost the body’s immune system to recognize and fight cancer more effectively. This dual action could potentially offer a more powerful response against aggressive prostate cancer types, such as neuroendocrine and aggressive variant prostate cancers, offering hope for patients with these challenging conditions.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants with aggressive prostate cancer types, such as neuroendocrine prostate cancer (NEPC), will receive a combination of the drugs nivolumab, ipilimumab, cabazitaxel, and carboplatin. Earlier studies have shown that this combination may reduce tumors in men with these aggressive cancer types. Nivolumab and ipilimumab are immunotherapy drugs that enhance the body's immune response against cancer cells, while cabazitaxel and carboplatin are chemotherapy drugs that target and kill fast-growing cancer cells. Although the highest level of evidence for treating these aggressive cancers is not yet available, these drugs have shown some success in various cancer treatments. Ongoing research aims to better understand how this combination works specifically for NEPC and similar aggressive cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Andrew Armstrong, MD, ScM

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04709276

NCT04709276 | A Study of Chemoimmunotherapy for the ...

The purpose of this study is to evaluate the safety and efficacy of a combination of nivolumab, ipilimumab, cabazitaxel and carboplatin in men with ...

2.

mdanderson.org

mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0816.html

A phase II, single arm study of chemoimmunotherapy for ...

The purpose of this study is to evaluate the safety and efficacy of a combination of nivolumab, ipilimumab, cabazitaxel and carboplatin in men with ...

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04347

Chemoimmunotherapy for the Treatment of Men with ...

This phase II trial tests whether chemoimmunotherapy with nivolumab, ipilimumab, cabazitaxel and carboplatin works to shrink tumors in men with neuroendocrine ...

4.

urotoday.com

urotoday.com/conference-highlights/apccc-2024/151542-apccc-2024-how-to-treat-men-with-aggressive-variant-or-neuroendocrine-prostate-cancer.html

APCCC 2024: How to Treat Men with Aggressive Variant or ...

To date, there is no level 1 evidence to inform the choice of systemic therapy for these men with aggressive variant/neuroendocrine prostate cancer.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10536803/

Outcomes of Second-Line Therapies in Patients With ...

Metastatic neuroendocrine prostate cancer (NEPC) is a rare, aggressive disease with limited data on second-line treatment.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7765615/

Neuroendocrine and Aggressive-Variant Prostate Cancer

The outcome is poor, with a small case series reporting a mean survival of seven months (range 3–12) after completion of platinum-based ...