Trial Title:
Relugolix and Enzalutamide in Combination With Radiation Therapy for the Treatment of Very High Risk Prostate Cancer, OPTIMAL Trial
NCT ID:
NCT06499870
Condition:
Prostate Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Fluorides
Relugolix
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:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
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:
Drug
Intervention name:
Enzalutamide
Description:
Given PO
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
ASP9785
Other name:
MDV 3100
Other name:
MDV-3100
Other name:
MDV3100
Other name:
Xtandi
Intervention type:
Other
Intervention name:
Fluorine F 18 Piflufolastat
Description:
Undergo fluorine F 18 piflufolastat PET/MRI
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
18F-DCFPyL
Other name:
Fluorine F 18 DCFPyL
Other name:
Piflufolastat F 18
Other name:
Piflufolastat F-18
Other name:
Piflufolastat F18
Other name:
Pylarify
Intervention type:
Radiation
Intervention name:
Image Guided Radiation Therapy
Description:
Undergo IGRT
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
IGRT
Other name:
image-guided radiation therapy
Other name:
Image-Guided Radiotherapy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo PET/MRI
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
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:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/MRI
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Intervention type:
Drug
Intervention name:
Relugolix
Description:
Given PO
Arm group label:
Treatment (relugolix, enzalutamide, IGRT)
Other name:
N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea
Other name:
Orgovyx
Other name:
Relumina
Other name:
TAK 385
Other name:
TAK-385
Other name:
TAK385
Summary:
This phase II trial tests how well relugolix and enzalutamide, in combination with
radiation therapy, works in treating patients with very high risk prostate cancer.
Relugolix is a form of androgen deprivation therapy. It prevents the release of
testosterone, a hormone required to sustain prostate growth. Reducing testosterone levels
may inhibit the proliferation of prostate tumor cells that need testosterone to grow.
Enzalutamide is an androgen receptor signaling inhibitor. It inhibits the activity of
prostate tumor cell receptors, which may reduce proliferation of prostate tumor cells.
Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer
cells and shrink tumors. Adding relugolix and enzalutamide to radiation therapy may be
more effective at treating patients with very high risk prostate cancer than giving any
of these treatments alone.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the efficacy of radiation therapy (RT) with androgen deprivation therapy
(ADT) (relugolix) and an androgen receptor signaling inhibitor (enzalutamide), for a
total duration of 18 months, in patients with National Comprehensive Cancer Network
(NCCN) very high-risk prostate cancer, as determined by a 2-year biopsy positivity rate.
SECONDARY OBJECTIVES:
I. To determine the 4-year disease free survival (DFS) (biochemical failure of prostate
specific antigen [PSA] nadir +2ng/mL, local or regional recurrence, distant metastasis,
or death from any cause).
II. To evaluate testosterone recovery.
EXPLORATORY OBJECTIVES:
I. To evaluate impact on patient-reported health-related quality of life utilizing (1)
Expanded Prostate Cancer Index Composite, EPIC-26 and (2) European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLC-C30).
II. To investigate a relationship between magnetic resonance imaging (MRI)-positron
emission tomography (PET) radiomic response (baseline and after neoadjuvant therapy)
correlated with pathologic and disease control endpoints.
OUTLINE:
Patients receive relugolix orally (PO) once daily (QD) and enzalutamide PO QD on days
1-28 of each cycle. Cycles repeat every 28 days for up to 18 months in the absence of
disease progression or unacceptable toxicity. After 4 months of treatment with relugolix
and enzalutamide, patients begin image-guided radiation therapy (IGRT) per standard of
care. Patients also undergo fluorine F 18 piflufolastat PET/MRI and CT on the trial,
undergo collection of blood samples throughout the trial, and undergo biopsy during
follow up.
After completion of study treatment, patients are followed up every 3-6 months for up to
30 months (48 months after study registration).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically confirmed prostate adenocarcinoma consistent with
NCCN very-high-risk (VHR) prostate cancer defined with at least one of the
following:
- cT3b-cT4 (American Joint Committee on Cancer [AJCC] 9.0)
- > 4 cores with grade group 4 or 5 prostate cancer
- Primary gleason pattern 5
- 2 or 3 NCCN high-risk features.
- Patients with involved pelvic lymph nodes below the common iliac bifurcation will be
allowed as long as the criteria for VHR (very-high risk) are met
- Patients must be age ≥ 18 years
- Patients must have testosterone > 50 ng/dL within 90 days prior to registration
- Note: Prior androgen deprivation (gonadotrophin releasing hormone [GnRH] analog
and/or non-steroidal antiandrogen) therapy is allowed provided that it is less
than 60 days of prior total duration and that serum testosterone concentration
must be ≥ 50 ng/dL prior to enrollment; 5-alpha reductase inhibitors will not
impact eligibility, but must be discontinued prior to starting protocol
treatment
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance
status of 0-2
- Leukocytes (white blood cells [WBC]) ≥ 2,500/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Hemoglobin (Hgb) ≥ 8 g/dL
- Platelets (PLT) ≥ 80,000/mcL
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) ≤
3 x institutional upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x
institutional ULN
- Creatinine ≤ institutional ULN
- Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2
- Estimated GFR (eGFR) is estimated GFR calculated by the abbreviated
Modification of Diet in Renal Disease (MDRD) equation
- For patients with a known history of human immunodeficiency virus (HIV), infected
patients on effective anti-retroviral therapy must have a viral load undetectable
for 3 months prior to registration with a CD4 count of ≥ 200 cells/μL. Note also
that HIV testing is not required for eligibility for this protocol as it is
self-reported
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be better than class III
- Patients must not have contraindications to magnetic resonance (MR) imaging and be
able to lie flat and still for approximately 30-40 minutes and be able to tolerate
PET/CT imaging and radiation therapy treatment planning and delivery
- Patients with female partners of reproductive potential must agree to use effective
contraception during treatment with and for 3 months after the last dose. Male
patients must use a condom during sex with a pregnant woman
- Patients must have the ability to understand and the willingness to sign a written
informed consent document and comply with the study requirements
Exclusion Criteria:
- Patients with definitive clinical or radiologic evidence of metastatic disease
- Patients with prior invasive malignancy (except non-melanomatous skin cancer
carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the
bladder, or stage I completely resected melanoma) unless disease free for a minimum
of 2 years
- Prior radiotherapy that would result in overlap of radiation therapy fields
- Patients who have a history of any of the following:
- History of documented inflammatory bowel disease
- Symptomatic congestive heart failure (New York Heart Association Functional
Classification III/IV) within 4 months prior to registration
- Unstable angina pectoris requiring hospitalization within the last 4 months
prior to registration
- History of seizure disorder or condition that may yield a high risk of seizure
(e.g., prior cortical stroke or significant brain trauma)
- Psychiatric illness/social situations that would limit compliance with study
requirements
- History of repeated falls and fractures over the past 12 months that in the
opinion of the treating investigator would put the patient at risk for poor
bone outcomes from androgen receptor targeted therapy
- Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or
study endpoints
- Patients with the inability to take oral medication OR have malabsorption
syndrome or any other uncontrolled gastrointestinal condition (eg, nausea,
diarrhea, vomiting) that might impair the bioavailability of enzalutamide and
relugolix
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
312-695-0990
Email:
cancer@northwestern.edu
Investigator:
Last name:
Sean Sachdev, MD
Email:
Principal Investigator
Start date:
September 6, 2024
Completion date:
November 19, 2032
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06499870
