Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors

NCT04126070 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-384
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Prostate Adenocarcinoma; Hormone Sensitive Prostate Cancer; Metastasis Prostate Adenocarcinoma

Keywords

Hormone Sensitive Prostate Cancer; Prostate Adenocarcinoma; Metastasis Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Prostate Specific Antigen (PSA) Less Than or Equal to 0.2 ng/mL at 7 Months From Start of Chemoimmunotherapy

  Summarized as percentage with 80% two-sided exact binominal confidence interval (CI) for each cohort

  7 months from the start of chemoimmunotherapy

Secondary Outcomes (7)

• Percentage of Subjects With PSA Less Than or Equal to 0.2 ng/mL During the Chemoimmunotherapy Combination

  From the start of chemoimmunotherapy until the end of treatment or initiation of new anti-cancer therapy, whichever occurred first, for a maximum duration of 2 years.

• Best Objective Response Rate in Subjects With Measurable Disease Per RECIST 1,1 Criteria

  From the start of chemoimmunotherapy until the end of treatment or initiation of new anti-cancer therapy, whichever occurred first, for a maximum duration of 2 years.

• Overall Survival Rate at 3-years

  Time from the start of chemoimmunotherapy to death due to any cause, or censored at date last known alive, up to 3-years

• Castration Resistant Disease-free Rate at 12 Months

  Time from the chemoimmunotherapy initiation to date of documented clinical or serological progression with castrate-level testosterone <50 ng/dL, or censored at date of last disease assessment before the start of new anti-cancer therapy, up to 12 months

• Clinical Progression Free Rate at 7 Months

  Time from the chemoimmunotherapy initiation to documented clinical or radiographic progression per RECIST 1.1 criteria, or censored at the date of last disease assessment before the start of new anti-cancer therapy, up to 7 months

Study Arms (3)

COHORT 1: DNA damage repair defects (DDRD) +/- Inflamed Tumor

EXPERIMENTAL

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.

Drug: Androgen Deprivation Therapy; Drug: Nivolumab; Drug: Docetaxel

COHORT 2: Inflamed Tumor without DNA repair defects (DDRD)

EXPERIMENTAL

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.

Drug: Androgen Deprivation Therapy; Drug: Nivolumab; Drug: Docetaxel

COHORT 3: Biomarker Negative

EXPERIMENTAL

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

Drug: Androgen Deprivation Therapy; Drug: Nivolumab; Drug: Docetaxel

Interventions

Androgen Deprivation Therapy DRUG

Given per standard care for duration of study. Regimens include Leuprolide (Lupron Depot) intramuscularly every 3 months, Goserelin acetate (Zoladex) subcutaneously every 4 weeks, or degarelix (Firmagon) subcutaneously every month per standard of care.

Also known as: Leuprolide, Lupron Depot, Goserelin acetate, Zoladex, Degarelix, Firmagon

COHORT 1: DNA damage repair defects (DDRD) +/- Inflamed Tumor; COHORT 2: Inflamed Tumor without DNA repair defects (DDRD); COHORT 3: Biomarker Negative

Nivolumab DRUG

Given once per every 3 weeks for cycle 1-6 intravenously and then every 4 weeks during subsequent cycles, at predetermined dosage; up to 28 cycles total.

COHORT 1: DNA damage repair defects (DDRD) +/- Inflamed Tumor; COHORT 2: Inflamed Tumor without DNA repair defects (DDRD); COHORT 3: Biomarker Negative

Docetaxel DRUG

Given once every 3 weeks intravenously at pre determined dosage for cycle 1-6.

Also known as: Taxotere

COHORT 1: DNA damage repair defects (DDRD) +/- Inflamed Tumor; COHORT 2: Inflamed Tumor without DNA repair defects (DDRD); COHORT 3: Biomarker Negative

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed histologically confirmed prostate adenocarcinoma within 6 months prior to study registration with evidence of high-volume distant metastasis on conventional imaging
• Distant metastasis is defined by non-regional lymph node(s) metastasis (M1a), bone metastasis (M1b), and/or other site(s) of metastatic disease (M1c).
• Conventional imaging consists of CT, MRI or radionuclide bone scan
• High volume of disease is defined by presence of four or more bone lesions with at least one beyond the vertebral bodies or pelvis or any site of visceral metastasis.
• Age ≥18 years
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Subjects with ECOG performance status of 2 are only eligible if the performance status decline is attributed to metastatic prostate cancer
• Serum PSA \> 4.0 ng/mL before initiation of ADT
• Serum testosterone \> 100 ng/dL before initiation of ADT
• Subjects whose testosterone level is unknown before initiation of ADT may be allowed after discussion with Sponsor-Investigator.
• Grade ≤ 1 peripheral neuropathy, defined as asymptomatic or paresthesia and/or decreased deep tendon reflexes is allowed.
• Subjects must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500 /mcL
• Platelets ≥100,000 /mcL
• 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

You may not qualify if:

• Subjects must not have received prior ADT (LHRH analogue +/- antiandrogen), chemotherapy, or immunotherapy for prostate cancer. The following exception is allowed:
• Subjects who have initiated ADT prior to study registration and are able to complete biomarker pre-screening, cohort allocation, and start C1D1 study chemoimmunotherapy ≤120 days from initiation of ADT are allowed
• The 120-day window commences at the start of either the antiandrogen agent or LHRH analogue, whichever is earlier
• Antiandrogens (e.g., bicalutamide or flutamide) may be used in addition to LHRH analogue ≤60 days before initiation of LHRH analogue to cover the testosterone surge associated with certain LHRH agonists but must be discontinued prior to study registration
• Second-generation hormonal agents (e.g., abiraterone acetate) are not allowed
• Subjects must not have undergone prostatectomy
• Prostate radiation is allowed before or after study enrollment and may be delivered concurrently with study chemoimmunotherapy, per provider discretion, assuming adequate prostate biopsy tissue is collected before prostatic radiation
• Metastasis-directed radiation is allowed before or after study enrollment and may be delivered concurrently with study chemoimmunotherapy, per provider discretion
• Subjects who are receiving any other investigational agents
• Any previous treatment with a PD-1 or PD-L1 inhibitor
• Subjects with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel (including any drugs formulated with polysorbate 80), nivolumab, or LHRH analogue (e.g., leuprolide, goserelin acetate, degarelix)
• History of another primary malignancy, except for:
• Malignancy treated with curative intent and with no known active disease for ≥2 years before the first dose of study treatment and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Sponsors & Collaborators

• Xiao X. Wei, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of California, San Diego

La Jolla, California, 92093, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21218, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Interventions

Androgen Antagonists; Leuprolide; Goserelin; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Nivolumab; Docetaxel

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Xiao X. Wei, MD,
• Organization: Dana-Farber Cancer Institute

xiaox_wei@dfci.harvard.edu

(617) 632-4524

Study Officials

• Xiao X Wei, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 14, 2019
• Study Start: May 11, 2020
• Primary Completion: July 29, 2025
• Study Completion: June 30, 2026
• Last Updated: May 27, 2026
• Results First Posted: May 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (6)