Clinical Trials /

REGN2810 Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer

NCT03951831

Description:

The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, androgen deprivation therapy (ADT), and docetaxel in patients with newly metastatic, hormone-sensitive prostate cancer (mHSPC), using a primary endpoint of undetectable prostate-specific antigen (PSA) at 6 months, defined from start of combination therapy (week 10) until 6 months (week 37).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: REGN2810 Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer
  • Official Title: Phase II, Open-label, Single-center Study Evaluating Safety and Activity of Androgen Deprivation Therapy Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Clinical Trial IDs

  • ORG STUDY ID: AAAS1863
  • NCT ID: NCT03951831

Conditions

  • Prostate Cancer Metastatic

Interventions

DrugSynonymsArms
REGN2810CemiplimabADT Followed by Chemoimmunotherapy
DegarelixFirmagonADT Followed by Chemoimmunotherapy
Leuprolide AcetateLupronADT Followed by Chemoimmunotherapy
DocetaxelTaxotereADT Followed by Chemoimmunotherapy

Purpose

The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, androgen deprivation therapy (ADT), and docetaxel in patients with newly metastatic, hormone-sensitive prostate cancer (mHSPC), using a primary endpoint of undetectable prostate-specific antigen (PSA) at 6 months, defined from start of combination therapy (week 10) until 6 months (week 37).

Detailed Description

      The slow progress for notable trials in metastatic, hormone-sensitive disease is attributed
      to the long duration of follow-up required, as well as the focus on time-to-event end points,
      i.e. overall survival, in clinical trial design. These landmark trials (CHAARTED, STAMPEDE,
      LATITUDE), which used overall survival as their endpoints, required, on average, 10 years
      from start of trial to first peer-reviewed publication. Given the challenge of using
      traditional measures of response (RECIST criteria) when designing prostate cancer clinical
      trials, the Prostate Cancer Working group 2 (PCWG2) made trial-design recommendations. One
      was to separate treatment outcomes into early measures of response and later time-to-event
      measures of progression. The goal is to shift the trial objective to capture and reflect the
      actual effect of the tested treatment and, in doing so, provide a more timely drug
      development milieu for the metastatic patient. These early measure of response end points,
      such as undetectable PSA with testosterone recovery, are now being actively integrated into
      clinical trial design.
    

Trial Arms

NameTypeDescriptionInterventions
ADT Followed by ChemoimmunotherapyExperimentalREGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.
  • REGN2810
  • Degarelix
  • Leuprolide Acetate
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent for the trial.

          2. Age ≥18 years of age on day of signing informed consent.

          3. Have life expectancy > 12 months.

          4. Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group
             (ECOG) Performance Scale.

          5. Have histologically or cytologically confirmed prostate cancer. Rarely pathology is
             not available but if clinical situation confirms prostate cancer (such as prior
             response to androgen ablation) pathology is not required and patient can be enrolled
             after discussed with study Principal Investigator (PI).

          6. Have metastatic disease that is either measurable or evaluable (non-measurable).

          7. Have evaluable (non-measurable) or measurable disease, based on RECIST 1.1, with at
             least one lesion amenable to biopsy.

          8. Have testosterone level ≥ 150ng/dL.

          9. Have not been on androgen deprivation therapy or novel hormonal agents (e.g.,
             abiraterone, enzalutamide, apalutamide) for at least 6 months prior to enrollment in
             trial and must not have exceeded 24 months of therapy and have shown to have no
             evidence of disease (PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy and <
             0.5 ng/dL and not have doubled above nadir after radiation therapy plus hormonal
             therapy) at least 12 months after completing adjuvant or neoadjuvant hormonal therapy
             in order to confirm hormone sensitive state.

         10. Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.

         11. Have not had prior surgical orchiectomy.

         12. Have not received palliative radiation within 14 days of starting ADT on study
             treatment.

         13. Have adequate organ and marrow function as defined below:

               -  Leukocytes ≥3,000/microliters (mcL)

               -  Absolute Neutrophil Count ≥1,500/mcL

               -  Platelets ≥100,000

               -  Hemoglobin ≥ 8.0g/dL (without transfusion in past 2 weeks)

               -  Prothrombin time (PT)/international normalized ratio (INR), partial
                  thromboplastin time (PTT) ≤ 1.5 upper limit of normal (ULN) (except if on
                  therapeutic anticoagulation in which case the patient can be enrolled if stable
                  and anti-coagulation levels are appropriate for their condition per good clinical
                  practice).

               -  Aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT)(SGPT) ≤2.5
                  × institutional ULN

               -  Total bilirubin within normal institutional limits. Note: Patients with
                  hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin
                  metabolism (e.g. Gilbert's syndrome) will be eligible at the discretion of the
                  treating physician and/or the principal investigator.

               -  Creatinine clearance of ≥ 30 mL/min. Creatinine clearance (CrCl) should be
                  calculated at screening using the Cockcroft-Gault formula.

         14. Agree to undergo serial tumor biopsies, unless medically contraindicated in the
             opinion of the treating physician, and discussed with the principal investigator

         15. The effects of REGN2810 on the developing human fetus are unknown. For this reason and
             because REGN2810 agents [as well as other therapeutic agents used in this trial] are
             known to be teratogenic, men treated or enrolled on this protocol must also agree to
             use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of REGN2810 administration. Should a
             woman become pregnant or suspect she is pregnant while her partner is participating in
             this study, she should inform her treating physician immediately.

        Exclusion Criteria:

        The subject must be excluded from participating in the trial if the subject:

          1. Received ADT or other hormonal agents within 6 months prior to entering the study or
             in the metastatic setting.

          2. Received prior immunotherapy (including inhibitors of programmed cell death protein 1
             (anti-PD-1), anti-PD-L1, anti-CTLA4, or Sipuleucel-T).

          3. Received prior chemotherapy for prostate cancer treatment.

          4. Received radiation within 2 weeks prior to entering study.

          5. Is receiving any other investigational agents concurrently.

          6. Had a solid organ or hematologic transplant.

          7. Has active autoimmune disease that has required systemic treatment in past 2 years
             (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive
             drugs).

          8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          9. Has a diagnosed additional malignancy within 2 years prior to first dose of trial
             treatment with the exception of curatively treated basal cell carcinoma of the skin or
             squamous cell carcinoma of the skin.

         10. Has a known history of, or any evidence of, interstitial lung disease or active
             noninfectious pneumonitis.

         11. Peripheral neuropathy must be ≤ grade 1.

         12. Has an active infection requiring systemic therapy.

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

         14. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         15. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

         16. Has untreated active Hepatitis B (HBV).

         17. Has dual infection with HBV/Hepatitis C Virus (HCV) or other hepatitis combinations at
             study entry.

         18. Has received a live vaccine within 30 days of planned start of study therapy (Cycle 1,
             Day 1). Note: The killed virus vaccines used for seasonal influenza vaccines for
             injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live
             attenuated vaccines and are not allowed.

         19. Patients with a history of severe hypersensitivity reaction to docetaxel or other
             drugs formulated with polysorbate 80 must be excluded.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Subjects Achieving Undetectable PSA at 6 months after Combination Treatment
Time Frame:6 months
Safety Issue:
Description:The percentage of subject achieving undetectable PSA levels at 6 months after the combination will use measured to determine safety and activity of combined hormonal chemoimmunotherapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mark Stein

Trial Keywords

  • Cancer
  • Chemoimmunotherapy
  • Prostate Cancer

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