Trial Title:
Pembrolizumab With Androgen Deprivation Therapy and Radiotherapy for the Treatment of Patients With High Risk Localized Prostate Cancer
NCT ID:
NCT06528210
Condition:
High Risk Prostate Carcinoma
Localized Prostate Adenocarcinoma
Stage I Prostate Cancer AJCC v8
Stage II Prostate Cancer AJCC v8
Stage III Prostate Cancer AJCC v8
Conditions: Official terms:
Prostatic Neoplasms
Pembrolizumab
Leuprolide
Goserelin
Bicalutamide
Triptorelin Pamoate
Hormones
Relugolix
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gonadotropin Releasing Hormone Agonists and Antagonists
Description:
Given PO, IM, Sub-Q injection or Sub-Q implant
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
GnRH Antagonist
Other name:
Gonadotropin Releasing Hormone Inhibitor
Other name:
Leuprolide
Other name:
Goserelin
Other name:
Triptorelin
Other name:
Degarelix
Other name:
Relugolix
Intervention type:
Drug
Intervention name:
Bicalutamide
Description:
Given PO
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
Casodex
Other name:
Cosudex
Other name:
ICI 176,334
Other name:
ICI 176334
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo prostate biopsy
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
BCD-201
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
Pembrolizumab Biosimilar QL2107
Other name:
QL2107
Other name:
SCH 900475
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary study
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Intervention type:
Radiation
Intervention name:
Radiation Therapy
Description:
Undergo radiation therapy
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
Cancer Radiotherapy
Other name:
Energy Type
Other name:
ENERGY_TYPE
Other name:
Irradiate
Other name:
Irradiated
Other name:
Irradiation
Other name:
Radiation
Other name:
Radiation Therapy, NOS
Other name:
Radiotherapeutics
Other name:
Radiotherapy
Other name:
RT
Other name:
Therapy, Radiation
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (Pembrolizumab, ADT, radiotherapy)
Other name:
Bone Scintigraphy
Summary:
This phase II trial tests how well pembrolizumab along with standard of care androgen
deprivation therapy, with bicalutamide and gonadotropin releasing hormone agonist, and
radiotherapy for the treatment of patients with high risk prostate cancer that has not
spread to other parts of the body (localized). A monoclonal antibody, such as
pembrolizumab, is a type of protein that can bind to certain targets in the body, such as
molecules that cause the body to make an immune response (antigens). Bicalutamide is in a
class of medications called androgen receptor inhibitors. It works by blocking the
effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor
cells. Gonadotropin-releasing hormone agonists prevent the body from making luteinizing
hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles
to stop making testosterone (a male hormone) in men and may stop the growth of prostate
cancer cells that need testosterone to grow. Radiation therapy uses high energy x-rays,
particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving
pembrolizumab with androgen deprivation therapy and radiotherapy may kill more tumor
cells in patients with high risk localized prostate cancer.
Detailed description:
PRIMARY OBJECTIVES:
I. Determine the rate of prostate biopsy positivity at 6 months (mo.) in patients
receiving pembrolizumab plus androgen deprivation therapy (ADT) in combination with
radiotherapy.
II. Determine the safety of pembrolizumab in combination with ADT and radiotherapy.
SECONDARY OBJECTIVES:
I. Compare 6-month post-treatment biopsy positive rate in patients stratified by
pre-treatment prostate infiltrating T-cell PD-1 and PD-L1 expression.
II. Measures changes in health related quality of life (HRQOL). III. Determine the rate
of grade 3 or higher Immune-related adverse events (irAEs).
IV. Determine the rate of biochemical relapse-free survival (bRFS) stratified by tumor
PD-1 and PD-L1 expression.
EXPLORATORY OBJECTIVES:
I. Determine the time to cancer-directed treatment in subjects undergoing experimental
treatment.
II. Determine the 5-year rate of biochemical relapse-free survival ([bRFS,] i.e. prostate
specific antigen [PSA] > nadir + 2 ng/mL) III. Determine the nadir biochemical response
rate (nadir PSA ≤ 0.5 ng/mL) IV. Determine the clinical and bRFS at five years. V. Report
safety and tolerability of pembrolizumab, defined as pembrolizumab related adverse event
of any grade and drug dose modification.
VI. Determine metastases-free survival based on conventional imaging (not positron
emission tomography [PET] based).
VII. Determine the serum castration recovery rate (testosterone above 50 ng/dL) VIII.
Determine the serum testosterone recovery rate (testosterone above 200 ng/dL) IX. Assess
the effect of pembrolizumab combined with ADT + radiation therapy (RT) on serum, blood
and tissue markers of the immune response.
X. Correlate changes in markers of inflammatory response with clinical outcomes including
post-treatment biopsy rate, PSA response and tumor free survival.
XI. Correlate baseline prostate specific membrane antigen (PSMA) scan findings with
efficacy endpoints.
XII. Changes from pre- to post-treatment serum, peripheral blood mononuclear cells
(PBMC), blood, microbial and tissue markers of the immune response.
XIII. Correlation of changes in markers of inflammatory response with clinical outcomes
including biopsy-complete response, PSA response and disease free survival.
XIV. Determine the rate of local tumor eradication at 12 months for those who had
persistent tumor at 6 months.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle.
Cycles repeat every 3 weeks for 51 weeks in the absence of disease progression or
unacceptable toxicity. Patients receive standard of care GNRH agonist therapy for a total
of 24 months, bicalutamide orally (PO) once per day (QD) for 6 months or up to 24 months
per the discretion of the treating physician and radiation therapy per standard of care.
Treatment is given in the absence of disease progression or unacceptable toxicity.
Patients undergo bone scan and/or computed tomography (CT) scan/ magnetic resonance
imaging (MRI) during screening and prostate biopsy and blood sample collection throughout
the study.
After completion of study therapy, patients are followed up at 30 days and yearly
thereafter.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants who are at least 18 years of age on the day of signing informed consent
with newly diagnosed histologically confirmed non-metastatic adenocarcinoma of the
prostate (regional spread as defined by National Comprehensive Cancer Network [NCCN]
guidelines is allowed) will be enrolled in this study with any one of the following
three high risk features:
- Gleason grade > 8-10
- PSA > 20 ng/ml
- Clinical stage T3a or T3b (T4 not allowed, see exclusion criteria)
- Participants must agree to use a contraception as detailed in the protocol during
the treatment period and for at least 12 months plus an additional 90 days (a
spermatogenesis cycle) after the last dose of study treatment and refrain from
donating sperm during this period
- The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial
- Archival tumor tissue sample or newly obtained [core, incisional or excisional]
biopsy of a tumor lesion not previously irradiated has been provided.
Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 30 days prior to the first dose of
study intervention
- Absolute neutrophil count (ANC) ≥ 1500/µL. (Specimens must be collected within 10
days prior to the start of study intervention)
- Platelets ≥ 100 000/µL. (Specimens must be collected within 10 days prior to the
start of study intervention)
- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L. (Specimens must be collected within 10 days
prior to the start of study intervention)
- Criteria must be met without erythropoietin dependency and without packed red
blood cell (pRBC) transfusion within last 2 weeks
- Creatinine OR measured or calculated creatinine clearance (CrCl) (glomerular
filtration rate [GFR] can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR
≥ 30 mL/min for participant with creatinine levels > 1.5 × institutional upper limit
of normal (ULN). (Specimens must be collected within 10 days prior to the start of
study intervention)
- Creatinine clearance (CrCl) should be calculated per institutional standard
- Total bilirubin ≤ 1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
bilirubin levels > 1.5 × ULN. (Specimens must be collected within 10 days prior to
the start of study intervention)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 ×
ULN (≤ 5 × ULN for participants with liver metastases). (Specimens must be collected
within 10 days prior to the start of study intervention)
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of
anticoagulants. (Specimens must be collected within 10 days prior to the start of
study intervention)
- Be willing to undergo a post-treatment prostate biopsy 6 months after completion of
therapy and optional re-biopsy at 12 months if 6-month biopsy was positive for
viable tumor
- PSA ≤ 100 ng/mL within 90 days of initiation of therapy. If PSA is repeated and
drops below 100 ng/mL without treatment, enrollment will be permitted
- If PSMA PET CT scan shows metastatic spread which is not detected on conventional
imaging (CT or bone scan), enrollment is allowed if tumor is considered low volume
(≤ 4 sites) with no visceral disease. (PSMA PET CT recommended but not required for
enrollment.)
- Must be willing to complete psychosocial and quality of life forms
- Criteria for known hepatitis B and C positive subjects.
- Hepatitis B and C screening tests are not required unless:
- Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection
- As mandated by local health authority
- Hepatitis B positive subjects
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible
if they have received HBV antiviral therapy for at least 4 weeks and have
undetectable HBV viral load prior to randomization.
- Participants should remain on anti-viral therapy throughout study intervention
and follow local guidelines for HBV anti-viral therapy post completion of study
intervention
- Participants with history of HCV infection are eligible if HCV viral load is
undetectable at screening.
- Participants must have completed curative anti-viral therapy at least 4 weeks
prior to randomization
Exclusion Criteria:
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX 40, CD137)
- Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to allocation
- Has received prior radiotherapy or radiation-related toxicities requiring
corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-central
nervous system (CNS) disease, with a 1-week washout, is permitted
- Has received a live vaccine or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of killed vaccines is allowed
- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in
situ of the bladder that have undergone potentially curative therapy are not
excluded
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to first dose of study intervention
- Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its
excipients
- Has active autoimmune disease that has required systemic treatment in the past 2
years except replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid)
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV
deoxyribonucleic acid [DNA]) and hepatitis C virus (defined as anti-HCV antibody
[Ab] positive and detectable HCV ribonucleic acid [RNA]) infection.
Note: Hepatitis B and C screening tests are not required unless:
- Known history of HBV and HCV infection
- As mandated by local health authority
- Plans to use abiraterone and prednisone in combination with radiotherapy. This
must be decided before enrollment
- Clinical T4 disease is excluded as the primary endpoint cannot be adequately
assessed for response in the surrounding tissue based on biopsy
- Evidence of metastatic, non-regional disease on conventional imaging, including
MRI, CT and bone scan
- Prostate size > 80 cc by MRI or ultrasound
- Subject has undergone a prior radical prostatectomy. Transurethral resection or
other surgical procedure for outlet obstruction allowed
- Subject has had major surgical procedures within 30 days of allocation
- Has not adequately recovered from major surgery or has ongoing surgical
complications
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the
study, such that it is not in the best interest of the participant to
participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Expecting to procreate within the projected duration of the study, starting
with the screening visit through 120 days after the last dose of trial
treatment
- Has had an allogenic tissue/solid organ transplant
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Contact:
Last name:
Mark G. Garzotto
Phone:
503-494-8311
Email:
garzotto@ohsu.edu
Investigator:
Last name:
Mark G. Garzotto
Email:
Principal Investigator
Start date:
August 1, 2024
Completion date:
June 1, 2028
Lead sponsor:
Agency:
OHSU Knight Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Oregon Health and Science University
Agency class:
Other
Source:
OHSU Knight Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06528210
