Androgen Deprivation Therapy (Leuprolide and Degarelix) and Chemoimmunotherapy (Cemiplimab and Docetaxel) for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer

Status: Active

Description

This phase II trial studies the side effects of androgen deprivation therapy (leuprolide and degarelix) and chemoimmunotherapy (cemiplimab and docetaxel) and to see how well they work in treating patients with hormone-sensitive prostate cancer that has spread to other places in the body (metastatic). Androgen can cause the growth of prostate cancer cells. Hormone therapy using leuprolide and degarelix may fight prostate cancer by blocking the use of androgen by the tumor cells. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The purpose of this study is to determine if the addition of immunotherapy to chemotherapy and androgen deprivation therapy, is safe and improves response to therapy.

Eligibility Criteria

Inclusion Criteria

  • Be willing and able to provide written informed consent for the trial
  • Have life expectancy > 12 months
  • Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) performance scale
  • 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)
  • Have metastatic disease that is either measurable or evaluable (non-measurable)
  • Have evaluable (non-measurable) or measurable disease, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with at least one lesion amenable to biopsy
  • Have testosterone level >= 150 ng/dL
  • 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
  • Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy
  • Have not had prior surgical orchiectomy
  • Have not received palliative radiation within 14 days of starting ADT on study treatment
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000
  • Hemoglobin >= 8.0 g/dL (without transfusion in past 2 weeks)
  • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 upper limit of normal (ULN) (except if on therapeutic anti-coagulation in which case the patient can be enrolled if stable and anti-coagulation levels are appropriate for their condition per good clinical practice)
  • Partial thromboplastin time (PTT) =< 1.5 ULN (except if on therapeutic anti-coagulation 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) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • 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
  • Agree to undergo serial tumor biopsies, unless medically contraindicated in the opinion of the treating physician, and discussed with the principal investigator
  • 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 6 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

  • Received ADT or other hormonal agents within 6 months prior to entering the study or in the metastatic setting
  • Received prior immunotherapy (including anti–PD-1, anti–PD-L1, anti-CTLA4, or Sipuleucel-T)
  • Received prior chemotherapy for prostate cancer treatment
  • Received radiation within 2 weeks prior to entering study
  • Is receiving any other investigational agents concurrently
  • Had a solid organ or hematologic transplant
  • 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). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose greater than 10mg/day of Prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • 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. Subjects with another malignancy diagnosed > 2 years prior to the first dose of trial medication who were treated with curative intent and are not undergoing active therapy will be eligible
  • Has a known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis
  • Peripheral neuropathy must be =< grade 1
  • Has an active infection requiring systemic therapy
  • 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
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). Note: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with REGN2810. In addition, these patients are at increased risk of lethal infections when treated with immunotherapy and marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Has untreated active hepatitis B. Note: To qualify for enrollment, antiviral therapy for hepatitis B virus (HBV) must be given for at least 3 months, and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Those on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout trial treatment. Those subjects who are hepatitis B virus core antibody (anti-HBc) (+), and negative for hepatitis B surface antigen (HBsAg), and negative for hepatitis B virus surface antibody (anti-HBs), and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis, but need close monitoring
  • Has dual infection with HBV/hepatitis C virus (HCV) or other hepatitis combinations at study entry
  • 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
  • Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 must be excluded

Locations & Contacts

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Mark Nathan Stein
Phone: 646-317-5290
Email: mns2146@columbia.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of cemiplimab (REGN2810) (anti-PD1 antibody), antiandrogen 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 after combination treatment (week 37).

SECONDARY OBJECTIVES:

I. To determine the time to development of castrate resistance after treatment with REGN2810 (anti-PD1 antibody), ADT, and docetaxel in newly mHSPC patients.

II. To evaluate radiographic response after treatment with REGN2810 (anti-PD1 antibody), ADT, and docetaxel in newly mHSPC patients.

EXPLORATORY OBJECTIVES:

I. To test whether immunotherapy changes the tumor microenvironment (TME) by coupling gene expression data with matched, full-length, paired clonotype sequence information pre- and post-treatment with REGN2810 (anti-PD1 antibody) and/or ADT using single cell ribonucleic acid (RNA) sequence (seq) analysis.

II. To understand if a treatment-driven immune signature exists with treatment of REGN2810 (anti-PD1 antibody) and/or ADT by evaluating pre- and post-treatment biopsy samples using single cell analysis.

III. To correlate gene expression data from metastases with circulating tumor deoxyribonucleic acid (DNA) during treatment course with REGN2810 (anti-PD1 antibody), ADT, and docetaxel.

IV. To determine the effects of combination REGN2810 (anti-PD1 antibody), ADT and docetaxel on cytokine levels including IL-1, IL-6, IL-8, IL-23, TNF-alpha, TGF-beta.

V. To determine if clinically meaningful increase in disease control is associated with an alteration in overall quality of life (QOL).

VI. Additional studies may be performed at later date.

OUTLINE:

Patients undergo biopsy at baseline and between weeks 3-4 or weeks 8-10. Patients also receive degarelix subcutaneously (SC) at week 1, leuprolide acetate SC every 3 months beginning weeks 4, cemiplimab IV every 3 weeks during weeks 4-55, and docetaxel IV on every 3 weeks during weeks 10-25. Treatment continues for up to 55 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, every 3 months up to 1 year, every 6 months up to 2 years and then annually up to 5 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Mark Nathan Stein

Trial IDs

Primary ID AAAS1863
Secondary IDs NCI-2019-05966
Clinicaltrials.gov ID NCT03951831