Nivolumab + Docetaxel + ADT for Metastatic Prostate Cancer

Recruiting at 5 trial locations

Overseen By Xiao X Wei, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Xiao X. Wei, MD

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: 7

Duration: 6 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a combination of hormonal therapy, chemotherapy, and immunotherapy as a possible treatment for metastatic hormone-sensitive prostate cancer. The names of the study drugs involved in this study are: * Androgen deprivation therapy (ADT) with a drug of your physician's choice. This may include leuprolide (Lupron), goserelin acetate (Zoladex), or degarelix (Firmagon). * Docetaxel * Nivolumab

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, it does mention that certain medications, like second-generation hormonal agents, are not allowed, and antiandrogens must be discontinued before registration. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination Nivolumab, Docetaxel, and ADT for metastatic prostate cancer?

Research shows that combining Docetaxel with Androgen Deprivation Therapy (ADT) improves survival in patients with metastatic prostate cancer compared to ADT alone. This suggests that adding Docetaxel to ADT is effective in treating this condition. ^{1 2 3 4 5}

Is the combination of Nivolumab, Docetaxel, and ADT safe for humans?

The combination of Docetaxel and androgen deprivation therapy (ADT) has been studied for prostate cancer and is generally considered safe, with some studies showing it can be safely combined with radiation therapy. However, specific safety data for the combination with Nivolumab is not provided in the available research. ^{1 6 7 8 9}

How is the drug combination of Nivolumab, Docetaxel, and ADT unique for treating metastatic prostate cancer?

This treatment is unique because it combines Nivolumab, an immunotherapy drug that helps the immune system fight cancer, with Docetaxel and Androgen Deprivation Therapy (ADT), which are already known to improve survival in advanced prostate cancer. The addition of Nivolumab may offer a novel approach by potentially enhancing the body's immune response against cancer cells. ^{1 4 5 6 10}

Research Team

Xiao Wei

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Men over 18 with newly diagnosed high-volume metastatic hormone-sensitive prostate cancer, not previously treated with ADT, chemotherapy or immunotherapy. They must have a good performance status and adequate organ function. Men must agree to use contraception during the study and for 7 months after.

Inclusion Criteria

Serum PSA > 4.0 ng/mL before initiation of ADT

Total bilirubin ≤1.5 × institutional upper limit of normal. Exception: Subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology) may be allowed after consultation with treating physician

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so on my behalf.

Exclusion Criteria

I am not allergic to docetaxel, nivolumab, or LHRH analogues.

I am taking oral dexamethasone before my docetaxel treatment.

I have not had hormone therapy, chemotherapy, or immunotherapy for prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive androgen deprivation therapy, docetaxel, and nivolumab. Nivolumab is given once every 3 weeks for cycle 1-6 and then every 4 weeks during subsequent cycles. Docetaxel is given once every 3 weeks for cycle 1-6.

6 months

6 visits (in-person) for cycles 1-6, then monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including time to clinical progression and overall survival.

up to 100 months

Treatment Details

Interventions

• Androgen Deprivation Therapy
• Docetaxel
• Nivolumab

Trial Overview The trial is testing a combination of hormonal therapy (ADT), chemotherapy (Docetaxel), and immunotherapy (Nivolumab) as potential treatments for advanced prostate cancer. Participants will receive these medications to see how well they work together.

Participant Groups

Group I: COHORT 3: Biomarker Negative Experimental Treatment 3 Interventions

After the screening procedures confirm participation in the research study. The participant will be given a study calendar for this trial. * Androgen Deprivation Therapy: Given per standard care for duration of study * Nivolumab: Given once per every 3 weeks for cycle 1-6 intravenously and then every 4 weeks during subsequent cycles, at predetermined dosage * Docetaxel: Given once every 3 weeks intravenously at pre-determined dosage for cycle 1-6

Group II: COHORT 2: Inflamed Tumor without DNA repair defects (DDRD) Experimental Treatment 3 Interventions

After the screening procedures confirm participation in the research study. The participant will be given a study calendar for this trial. * Androgen Deprivation Therapy: Given per standard care for duration of study * Nivolumab: Given once per every 3 weeks for cycle 1-6 intravenously and then every 4 weeks during subsequent cycles, at predetermined dosage * Docetaxel: Given once every 3 weeks intravenously at pre-determined dosage for cycle 1-6.

Group III: COHORT 1: DNA damage repair defects (DDRD) +/- Inflamed Tumor Experimental Treatment 3 Interventions

After the screening procedures confirm participation in the research study. The participant will be given a study calendar for this trial. * Androgen Deprivation Therapy: Given per standard care for duration of study * Nivolumab: Given once per every 3 weeks for cycle 1-6 intravenously and then every 4 weeks during subsequent cycles, at predetermined dosage * Docetaxel: Given once every 3 weeks intravenously at pre-determined dosage for cycle 1-6.

Androgen Deprivation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Who Is Running the Clinical Trial?

Xiao X. Wei, MD

Lead Sponsor

Trials

1

Recruited

60+

Xiao X. Wei

Lead Sponsor

Trials

1

Recruited

60+

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

In a study involving 376 patients with intermediate- or high-risk prostate cancer, six cycles of adjuvant docetaxel after radical radiotherapy did not improve biochemical disease-free survival compared to surveillance, with similar progression rates in both groups (31% for docetaxel vs. 28% for surveillance).

While 78% of patients completed all six cycles of docetaxel, the treatment was associated with a 16% incidence of febrile neutropenia, but no deaths were directly related to the docetaxel treatment, indicating a safety profile that did not translate into improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial. Kellokumpu-Lehtinen, PL., Hjälm-Eriksson, M., Thellenberg-Karlsson, C., et al.[2020]

In a study of 773 men with metastatic hormone-sensitive prostate cancer, the combination of docetaxel and androgen deprivation therapy (ADT) showed similar progression-free survival (PFS) and overall survival (OS) benefits across different age groups, indicating its efficacy regardless of age.

Older men (over 70 years) experienced a modest increase in the number of adverse events compared to younger men, suggesting that while the treatment is effective, careful consideration of potential side effects is crucial for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial. Li, EV., Siddiqui, MR., Weiner, AB., et al.[2022]

In a study of 173 men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with docetaxel plus androgen deprivation therapy (ADT), the median overall survival was 51.6 months, indicating that this treatment is effective in a real-world setting.

The study found that 46% of patients developed castration-resistant prostate cancer within one year, with a median time to this progression of 15.6 months, highlighting the need for ongoing monitoring and potential additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Docetaxel for Metastatic Hormone-sensitive Prostate Cancer in Clinical Practice. Lendorf, ME., Petersen, PM., Svendsen, AS., et al.[2022]

In a study of 153 patients with high-volume metastatic hormone-sensitive prostate cancer, combining docetaxel chemotherapy with androgen-deprivation therapy (ADT) significantly improved progression-free survival (16.9 months vs. 11.2 months for ADT alone) and resulted in a higher PSA response rate (42.9% vs. 13.3% achieving PSA <0.2 ng/ml within 12 months).

While the combination therapy showed promising efficacy, it also led to notable adverse effects, including neutropenia in 61.9% of patients, with 19% experiencing severe cases, indicating that while effective, close monitoring for side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis. Guo, Z., Lu, X., Yang, F., et al.[2022]

In a Phase I study involving 18 patients with high-risk prostate cancer, the addition of weekly docetaxel chemotherapy at a safe dose of 20 mg/m² to high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) was found to be safe, with no severe toxicities reported.

At a median follow-up of 2.2 years, the treatment resulted in a high biochemical progression-free survival rate of 94%, indicating promising efficacy for this triple-therapy regimen in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. Chen, RC., Rosenman, JG., Hoffman, LG., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial. [2020]

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

Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Department of Medicine; Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Johns Hopkins University, Baltimore; University of Wisconsin Carbone Cancer Center; School of Medicine and Public Health; Madison; Fox Chase Cancer Center, Temple University Health System, Philadelphia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis; Mayo Clinic, Rochester, MN; University Hospitals Case Medical Center, Seidman Cancer Center; Cleveland Clinic Taussig Cancer Institute; Both in Cleveland; University of Virginia Cancer Center, Charlottesville; Comprehensive Cancer Centers of Nevada, Las Vegas; Siteman Cancer Center, Washington University School of Medicine, St. Louis; NorthShore University Health System, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor; Rutgers Cancer Institute of New Jersey, New Brunswick.N Engl J Med. 2015 Aug 20;373(8):737-46. [Epub 2015 Aug 5]. doi: 10.1056/NEJMoa1503747. [2019]

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

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Chemotherapy in hormone-sensitive metastatic prostate cancer: Evidences and uncertainties from the literature. [2022]

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

Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy: A Randomized Clinical Trial. [2022]

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

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial. [2022]

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

Effectiveness of Docetaxel for Metastatic Hormone-sensitive Prostate Cancer in Clinical Practice. [2022]

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

Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis. [2022]

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

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies. [2022]