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Clinical Trial 20377

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT04126070

Phase: Phase II
Principal Investigator: Chahoud, Jad

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Study Title

A Phase 2 Multicohort Study of Nivolumab in Combination with Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone Sensitive Prostate Cancer Patients with DNA Damage Repair Defects or Inflamed Tumors


The goal of this study is to examine the activity and safety of hormonal therapy combined with docetaxel chemotherapy and nivolumab immunotherapy for hormone sensitive prostate cancer. The study is designed to enrich for patients whose tumors may be more most responsive to this treatment strategy. All patients will receive the same treatment of ADT combined with docetaxel chemotherapy and nivolumab immunotherapy.


Primary Objective: To determine the proportion of subjects with PSA less than or equal to 0.2 ng/mL at 12 months from start of treatment in each cohort Secondary Objective: To determine the proportion of subjects with PSA less than or equal to 0.2 ng/mL at 7 months To estimate overall survival (OS) To estimate time to castration resistance To estimate time to clinical progression To estimate time to prostate specific antigen (PSA) or serologic progression To determine the objective response rate in subjects with measurable disease To assess safety and tolerability to chemohormonal-immunotherapy in the upfront management of mHSPC



Immunotherapy; Therapy (NOS)


ADT (); BMS-936558 (Nivolumab); Firmagon (); Lupron (leuprolide acetate); Nivolumab (Opdivo); Taxotere (docetaxel); Zoladex (); docetaxel (); goserelin acetate (Zoladex)

Inclusion Criteria

  • Newly diagnosed histologically confirmed prostate adenocarcinoma within 4 months prior to study registration with evidence of 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.
  • Serum PSA > 4.0 ng/mL before initiation of ADT
  • Serum testosterone > 100 ng/dL before initiation of ADT
  • Grade > Participants must have adequate organ and marrow function as defined per protocol
  • Availability of adequate baseline prostate biopsy tissue for integral biomarker analysis and correlative studies, defined in protocol
  • Participants whose tumors harbor somatic or germline homozygous deletions and/or deleterious mutations in a DDR gene using OncoPanel will be assigned to Cohort 1, regardless of ImmunoProfile results
  • Participants whose tumors are PD-L1 positive and/or CD8+ T cell inflamed using ImmunoProfile without the presence of DDRD will be assigned to Cohort 2
  • Participants whose tumors do not harbor DDRD and are PD-L1 negative with low CD8+ T cell infiltration will be assigned to Cohort 3
  • Willingness to provide leftover metastatic biopsy tissue for correlative studies, if obtained for clinical purposes
  • Based on its mechanism of action and data from animal studies, nivolumab can cause fetal harm. For this reason non-sterilized men who are sexually active with a female partner of childbearing potential treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for 7 months after last dose of nivolumab administration
  • Ability to understand and the willingness to sign a written informed consent document, or have a legally authorized representative sign on the subject's behalf

  • Exclusion Criteria

  • Participants must not have received prior ADT (LHRH analogue antiandrogen), chemotherapy, or immunotherapy for prostate cancer. The following exception is allowed:
  • Participants 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
  • Antiandrogens may be used in addition to LHRH analogue ≤28 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
  • Participants 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
  • Participants who are receiving any other investigational agents
  • Any previous treatment with a PD-1 or PD-L1 inhibitor
  • Participants with known brain metastases
  • 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
  • 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
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Major surgical procedure as defined by the Site Investigator within 28 days prior to the first dose of chemoimmunotherapy
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • History of allogeneic bone marrow or organ transplantation
  • Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, with the following exceptions:
  • Vitiligo or alopecia
  • Hypothyroidism stable on hormone replacement
  • Chronic skin condition that does not require systemic therapy
  • Celiac disease controlled by diet alone
  • Participants with inactive disease in the last 5 years may be included but only after consultation with the study physician
  • Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg]), or hepatitis C (HCV)
  • Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible
  • Participants with positive HCV antibody are eligible if polymerase chain reaction is negative for HCV RNA
  • Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study chemoimmunotherapy, with the following exceptions:
  • Premedication for docetaxel with dexamethasone prior to docetaxel administration
  • Intranasal, inhaled, topical steroids, or local steroid injections
  • Other exclusion will apply per protocol

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