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

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ClinicalTrials.gov Identifier: NCT03951831
Recruitment Status : Recruiting
First Posted : May 15, 2019
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Mark Stein, Columbia University

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: REGN2810 Drug: Degarelix Drug: Leuprolide Acetate Drug: Docetaxel Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ADT Followed by Chemoimmunotherapy

REGN2810 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.

Drug: REGN2810
Cemiplimab (REGN 2810) is administered starting at week 4 at a dose of 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease.
Other Name: Cemiplimab

Drug: Degarelix
Degarelix is administered subcutaneously (SC) at a dose of 240mg once.
Other Name: Firmagon

Drug: Leuprolide Acetate
Leuprolide acetate is provided at a dose of 22.5mg SC every 3 months.
Other Name: Lupron

Drug: Docetaxel
Docetaxel is administered starting at week 10 at a dose of 75 mg/m2 every 21 days for up to 6 cycles.
Other Name: Taxotere




Primary Outcome Measures :
  1. Percentage of Subjects Achieving Undetectable PSA at 6 months after Combination Treatment [ Time Frame: 6 months ]
    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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03951831


Contacts
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Contact: Lisa Olmos, RN 212-342-5162 cancerclinicaltrials@cumc.columbia.edu
Contact: Mark Stein, MD (212) 304-5558 mns2146@cumc.columbia.edu

Locations
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United States, New York
Columbia University Irving Medical Center Recruiting
New York, New York, United States, 10032
Contact: Mark Stein, MD       mns2146@cumc.columbia.edu   
Principal Investigator: Mark Stein, MD         
Sponsors and Collaborators
Mark Stein
Regeneron Pharmaceuticals
Investigators
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Principal Investigator: Mark Stein, MD Associate Professor of Medicine

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Responsible Party: Mark Stein, Associate Clinical Professor of Medical Oncology, Columbia University
ClinicalTrials.gov Identifier: NCT03951831     History of Changes
Other Study ID Numbers: AAAS1863
First Posted: May 15, 2019    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Mark Stein, Columbia University:
Cancer
Chemoimmunotherapy
Prostate Cancer

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Genital Diseases, Male
Docetaxel
Leuprolide
Cemiplimab
Hormones
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Immunological