Trial Title:
Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations
NCT ID:
NCT05498272
Condition:
Prostate Cancer
BRCA1 Mutation
BRCA2 Mutation
Prostatic Adenocarcinoma
High-Risk Cancer
Conditions: Official terms:
Prostatic Neoplasms
Olaparib
Leuprolide
Goserelin
Triptorelin Pamoate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib
Description:
300 mg orally twice a day (D1-D30) for 6 Cycles (30 day Cycles)
Arm group label:
Investigational Group
Other name:
Lynparza
Intervention type:
Drug
Intervention name:
LHRH agonist
Description:
Total duration of therapy will be for 180 days with use of agent as per institutional
standards
Arm group label:
Investigational Group
Other name:
Goserelin
Other name:
Triptorelin
Other name:
Leuprolide
Summary:
Phase 2 open-label, single-arm clinical trial evaluating the efficacy and safety of
neoadjuvant olaparib + LHRH agonist administered for 6 months prior to radical
prostatectomy (RP) in men with unfavorable intermediate-risk or high-risk localized
prostate cancer. All patients must have confirmed germline or somatic select HRR
alterations. Germline and somatic mutation testing will be performed as part of
commercially available CLIA assays and will be validated on a uniform platform centrally
all patients retrospectively.
Eligible patients will receive treatment with olaparib + LHRH agonist. Following 6 months
of therapy, patients will undergo RP with mandatory lymph node dissection. The lymph node
dissection template will be at the discretion of the treating urologist. RP specimens
will undergo pathology blinded independent central review. Following RP, patients will be
followed for testosterone recovery and PSA progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in
this study:
- Written informed consent and HIPAA authorization for release of personal health
information prior to registration.
- Age ≥ 18 years at the time of consent.
- T stage 1-3 prostatic adenocarcinoma per AJCC staging manual Ed8.
- Histologically confirmed adenocarcinoma of the prostate without histological
variants comprising >50% of the sample. Patients with intraductal carcinoma are
eligible.
- Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be
obtained). Prostate biopsy must be within 7 months from registration. Less than 3
core biopsies are allowed if the patient has >1 cm or T3 disease on magnetic
resonance imaging (MRI).
- Localized unfavorable intermediate or high-risk prostate cancer patients. Patients
must have at least one of the following features:
- Gleason ≥ 4+3 (grade group 3, 4, 5) OR
- PSA > 20 ng/dL OR
- T3 disease NOTE: Patients with intraductal carcinoma are eligible independent
of Gleason score, PSA and T stage.
- Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D,
RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of
care CLIA based assay detection. Testing will be confirmed centrally but results of
central testing not required for enrollment.
- No evidence of metastatic disease as determined by radionuclide bone scan and
CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
- Participants must be candidates for RP and considered surgically resectable by
urologic evaluation.
- ECOG Performance Status of 0-1 within 28 days prior to registration.
- Demonstrate adequate organ function as defined below. All screening labs to be
obtained within 28 days prior to registration.
- White blood cell count ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 10 g/dL with no transfusion support in the past 28 days
- Platelets ≥ 100,000/mcL
- Aspartate aminotransferase, alanine aminotransferase ≤ 2.5×ULN, and total
bilirubin ≤ 1.5 x Institutional upper limit of normal
- Calculated creatinine clearance ≥ 51 mL/min based on Cockcroft-Gault formula or
24 hour urine. NOTE: See the protocol for Cockcroft-Gault formula or 24 hour
urine.
- Life expectancy≥ 16 weeks.
- Subjects must use a condom plus spermicide beginning prior to treatment Cycle 1 Day
1, during treatment and for 3 months after the last dose of olaparib when having
sexual intercourse with a pregnant woman or with a woman of childbearing potential.
Female partners of male patients should also use a highly effective form of
contraception if they are of childbearing potential. See protocol for additional
details.
- As determined by the enrolling physician or protocol designee, ability of the
subject to understand and comply with study procedures for the entire length of the
study.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
- Active infection requiring systemic therapy.
- Prior treatments not allowed: hormone therapy for prostate cancer including
orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide,
apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700,
galeterone, ketoconazole, and others), estrogens and radiation therapy. Prior
bicalutamide is allowed if taken for < 4 weeks prior to registration and there is a
washout period of 2 weeks prior to the initiation of study treatment. LHRH
agonist/antagonist therapy is allowed if begun within 4 weeks of registration. Prior
5-alpha reductase inhibitors are allowed but require a washout period of 2 weeks to
initiation of study treatment.
- Prior treatment with a PARP inhibitor.
- Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy including:
- tuberculosis (clinical evaluation that includes clinical history, physical
examination, and radiographic findings, and TB testing in line with local
practice).
- Known active hepatitis infection, positive hepatitis C antibody, hepatitis B
virus surface antigen or hepatitis B virus core antibody at screening. Testing
is not required unless there was a prior known positive hepatitis B or C test
or hepatitis is suspected at screening. Active hepatitis B virus (HBV) is
defined by a known positive HBV surface antigen (HBsAg) result. For patients
with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load
must be undetectable on suppressive therapy, if indicated. Patients with a
history of hepatitis C virus (HCV) infection must have been treated and cured.
For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Known to have tested positive for human immunodeficiency virus (HIV) unless
currently on effective anti-retroviral therapy with an undetectable viral load
within 6 months.
- Severe hepatic impairment (Child-Pugh Class C).
- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication.
- Pre-existing condition that warrants long-term corticosteroid use greater than the
equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical,
intra-articular steroids or inhaled corticosteroids are permitted.
- Active cardiac disease, defined as:
- Myocardial infarction within 6 months of study treatment.
- Uncontrolled angina within 3 months of study treatment.
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
subjects with history of congestive heart failure NYHA class 3 or 4 in the
past, or history of anthracycline or anthracenedione (mitoxantrone) treatment,
unless an echocardiogram performed within 3 months of the screening visit
results in a left ventricular ejection fraction that is ≥ 45%.
- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsade de pointes)
- Other clinically significant cardiovascular disease within 6 months of
registration.
- Uncontrolled, potentially reversible cardiac conditions, as judged by the
investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia,
congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances,
etc.), or patients with congenital long QT syndrome.
- Individuals with a history of another malignancy are not eligible if the cancer is
under active treatment or the cancer can be seen on radiology scans.
- Major surgery within 4 weeks from start of treatment. Subjects must have recovered
from any effects as the surgery as assessed by investigator discretion.
- Treatment with any investigational drug within 28 days prior to registration.
- Persistent toxicities Grade > 2 caused by previous cancer therapy (per Common
Terminology Criteria for Adverse Event (CTCAE)).
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML.
- Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include but are not limited to, uncontrolled ventricular arrhythmia, recent (within
3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial
bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any
psychiatric disorders that prohibits obtaining informed consent.
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment.
- Concomitant use of known strong CYP3A inhibitors. The required washout period prior
to starting olaparib is 2 weeks.
- Concomitant use of known strong or moderate CYP3A inducers. The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.
- Previous allogenic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT).
- Whole blood transfusions in the last 120 days prior to entry to the study (packed
red blood cells and platelet transfusions are acceptable, for timing refer to the
protocol).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California San Diego - Moores Cancer Center
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bianca Mogannam
Email:
bmogannam@health.ucsd.edu
Investigator:
Last name:
Rana R McKay
Email:
Principal Investigator
Facility:
Name:
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carolyn Chapman, RN
Email:
cchapma7@jhmi.edu
Contact backup:
Last name:
Sandra Moore-Cooper
Email:
mooresa@jhmi.edu
Investigator:
Last name:
Channing Paller, MD
Email:
Principal Investigator
Facility:
Name:
Columbia University Irving Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jillian Gray
Email:
jg4400@cumc.columbia.edu
Investigator:
Last name:
Karie Runcie, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christine Moon
Phone:
646-422-4600
Email:
moonc@mskcc.org
Investigator:
Last name:
Deaglan McHugh, MD
Email:
Principal Investigator
Facility:
Name:
Penn Medicine Abramson Cancer Center
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Louie
Email:
jennifer.louie2@pennmedicine.upenn.edu
Investigator:
Last name:
Naomi Balzar Haas, MD
Email:
Principal Investigator
Start date:
February 1, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Rana McKay, MD
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
University of California, San Diego
Agency class:
Other
Source:
Hoosier Cancer Research Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05498272
