Trial Title:
Effects of Relugolix vs Leuprolide on Cardiac Function in Patients With Prostate Cancer
NCT ID:
NCT06330805
Condition:
Prostate Adenocarcinoma
Stage IIB Prostate Cancer AJCC v8
Stage IIC Prostate Cancer AJCC v8
Conditions: Official terms:
Prostatic Neoplasms
Leuprolide
Relugolix
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and urine sample collection
Arm group label:
Arm 1 (leuprolide)
Arm group label:
Arm 2 (relugolix)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Other
Intervention name:
Contrast Agent
Description:
Given IV
Arm group label:
Arm 1 (leuprolide)
Arm group label:
Arm 2 (relugolix)
Other name:
Contrast
Other name:
Contrast Drugs
Other name:
contrast material
Other name:
Contrast Medium
Intervention type:
Drug
Intervention name:
Leuprolide
Description:
Given injection
Arm group label:
Arm 1 (leuprolide)
Other name:
Leuprorelin
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (leuprolide)
Arm group label:
Arm 2 (relugolix)
Other name:
Magnetic Resonance
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:
Other
Intervention name:
Physical Performance Testing
Description:
Undergo functional fitness tests
Arm group label:
Arm 1 (leuprolide)
Arm group label:
Arm 2 (relugolix)
Other name:
Physical Fitness Testing
Other name:
Physical Function Testing
Intervention type:
Drug
Intervention name:
Relugolix
Description:
Given PO
Arm group label:
Arm 2 (relugolix)
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
Summary:
This phase II trial compares the effect of relugolix to leuprolide on cardiac function
and performance in patients with prostate cancer. Androgen deprivation therapy (ADT) has
been a key component for the treatment of advanced prostate cancer for decades. The term
androgen deprivation therapy means lowering a man's testosterone. Long-term studies show
that ADT may contribute to a detriment to cardiac health and predisposes men to
developing cardiac diseases. Recent studies suggest that men taking relugolix for
treatment of prostate cancer may have a lower risk of developing cardiovascular problems,
but more studies are needed to understand this observation, and there are currently no
studies reporting the direct impact of ADT (relugolix, versus the more-commonly used
leuprolide) on cardiac function and outcomes.
Participants will receive definitive radiotherapy for unfavorable intermediate risk
prostate cancer and 6-month ADT (either relugolix or leuprolide). In addition,
participants will undergo the following:
1. Comprehensive cardiac and exercise testing before and after starting ADT
2. Completion of quality-of-life questionnaires at specific intervals during the study
period
3. Provide blood samples at specific intervals during the study period to test for
changes in steroid levels and certain biomarkers
Detailed description:
PRIMARY OBJECTIVES:
I. To quantify the physiologic alterations in cardiopulmonary function in men receiving
6-month relugolix verse (vs.) 6-month leuprolide with definitive radiation therapy (RT)
for unfavorable intermediate risk (UIR) clinically localized prostate cancer (PCa).
II. Cardiopulmonary and cardiac measures obtained from: 1) exercise stress cardiac
magnetic resonance imaging (MRI) perfusion, and 2) maximal rate of oxygen consumption
(VO2), include myocardial perfusion reserve index (MPRI), contractile reserve, myocardial
longitudinal relaxation time (T1) signal, longitudinal strain, circumferential strain,
VO2 maximum (max), and metabolic equivalents of exercise capacity (METs).
SECONDARY OBJECTIVES:
I. To quantify the impact of 6-month relugolix vs. leuprolide with definitive RT for UIR
PCa on quality of life (QoL) using Expanded Cancer Index Composite (EPIC)-26, European
Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
(EORTC QLQ-C30), European (Euro) Qol-5-Dimension 5-level (EQ-5D-5L), and Patient Reported
Outcomes Measurement Information System (PROMIS) Fatigue (Short Form 8a) patient-reported
outcome surveys, or similar tests.
II. To quantify the impact of 6-month relugolix vs. leuprolide on composite functional
tests of strength and balance using three tests: 1) Timed Up-and-Go, 2) 10-meter walk
time, and 3) grip strength.
III. To analyze body composition changes in response to 6-month relugolix vs. leuprolide
by using abdominal computed tomography (CT) or magnetic resonance imaging (MRI) to
quantitate abdominal/visceral fat and lean muscle mass with utilization of SliceOmatic
software.
EXPLORATORY OBJECTIVES:
I. To compare changes in serum steroid profiles (panel of 17 steroid hormone metabolites,
Ohio State University Comprehensive Cancer Center [OSUCCC Pharmacoanalytic Shared
Resource [PhASR]) before, during and after 6-month relugolix vs. 6-month leuprolide with
definitive RT for UIR PCa.
II. To compare changes in cardiometabolic biomarkers in the following three categories:
1) glycemic control parameters (fasting glucose, fasting insulin, and connecting
[C]-peptide), 2) lipid profiles (total cholesterol, triglyceride, low-density lipoprotein
[LDL], high-density lipoprotein [HDL], and leptin/adiponectin ratio), 3) markers of the
obesity-associated low-grade chronic inflammatory state (CRP, TGF-beta, and IL-6, and
novel related immunoregulators), and targeted or non- targeted metabolomics or proteomics
(by OSUCCC NPASR and PSR) depending on procurement of additional funds.
III. To compare the time course of recovery for hormonal and cardiometabolic markers
after completion of 6-month relugolix vs. 6-month leuprolide with definitive RT for UIR
PCa.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive definitive therapy for prostate cancer with ADT (leuprolide via
injection once every 3 months, for a total of 6 months) in the absence of disease
progression or unacceptable toxicity and definitive radiotherapy within 90 days of
starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo
exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing
before starting ADT and at 6 months after starting ADT. Patients also undergo blood and
urine sample collection throughout the study, as well as completion of quality-of-life
questionnaires.
ARM 2: Patients receive definitive therapy for prostate cancer with ADT (relugolix orally
once daily for a total of 6 months) in the absence of disease progression or unacceptable
toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive
gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI
perfusion and comprehensive exercise physiology testing before starting ADT and at 6
months after starting ADT. Patients also undergo blood and urine sample collection
throughout the study, as well as completion of quality-of-life questionnaires.
After completion of study treatment, patients are followed up at 1, 3, and 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Pathologically proven diagnosis of adenocarcinoma of the prostate within 270 days
prior to registration.
- Unfavorable intermediate risk prostate cancer, defined as having ALL the following
bulleted criteria:
- Has at least one intermediate risk factor (IRF):
- Prostate-specific antigen (PSA) 10-20 ng/mL
- Clinical stage tumor (T)2b-c (digital rectal exam [DRE] and/or imaging) by
American Joint Committee on Cancer (AJCC) 8th edition
- Gleason Score 7 (Gleason 3+4 or 4+3 [International Society of Urological
Pathology [ISUP] grade group 2-3])
- Has one or more of the following "unfavorable" intermediate-risk designators:
- > 1 IRF
- Gleason 4+3=7 (ISUP grade group 3)
- ≥ 50% of biopsy cores positive
- Biopsies may include "sextant" sampling of right/left regions of the
prostate, often labeled base, mid-gland and apex. All such "sextant"
biopsy cores should be counted. Men may also undergo "targeted"
sampling of prostate lesions (guided by MRI, ultrasound or other
approaches). A targeted lesion that is biopsied more than once and
demonstrates cancer (regardless of number of targeted cores involved)
should count as a single additional positive core sampled and
positive. In cases of uncertainty, count the biopsy sampling as
sextant core(s).
- Absence of high-risk features
- Appropriate stage based on the following diagnostic workup:
- History/physical examination within 120 days prior to registration
- Negative bone imaging (M0) with Tc-99m bone scan or fluciclovine (18F) sodium
fluoride (NaF) positron emission tomography (PET) within 120 days prior to
registration
- Clinically negative lymph nodes (N0) as established by conventional imaging
(pelvic +/- abdominal CT or MRI), within 120 days prior to registration (lymph
nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.0
cm in short axis and/or if biopsy is negative)
- Prostate specific membrane antigen (PSMA) or fluciclovine PET negative for
nodal or distant metastatic disease is an acceptable substitute for the above
bone and pelvic imaging
- Age ≥ 18
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 120 days
prior to registration.
- Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration.
- Absolute neutrophil ≥ 1,000 cells/mm^3 (within 120 days prior to registration)
- Hemoglobin ≥ 10 g/dL (within 120 days prior to registration)
- Platelet count ≥ 100,000 cells/mm^3 (within 120 days prior to registration)
- Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault Equation
(within 120 days prior to registration)
- For African American patients, CrCl ≥ 30 mL/min is estimated by the alternative
formula that takes race into account
- Total bilirubin: 1.5 ≤ institutional upper limit of normal (ULN) (within 120 days
prior to registration)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) ≤ 2.5 ×
institutional ULN (within 120 days prior to registration)
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial. Note: HIV testing is not required
for eligibility for this protocol.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating
acute or chronic infection would make the patient ineligible unless the viral load
becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B
(anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized
against hepatitis B).
- For 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.
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy.
- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information.
Exclusion Criteria:
- Previous radical surgery (prostatectomy) or any form of curative-intent ablation
whether focal or whole-gland (e.g., cryosurgery, High-intensity focused ultrasound
(HIFU), laser thermal ablation, etc.) for prostate cancer.
- Definitive clinical or radiologic evidence of metastatic disease (M1).
- Prior invasive malignancy (except non-melanomatous skin cancer) or hematologic
malignancy unless disease free for a minimum of 3 years.
- Prior radiotherapy to the prostate/pelvis region that would result in overlap of
radiation therapy fields.
- Previous bilateral orchiectomy.
- Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH)
agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist
(e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone
acetate). ADT started prior to study registration is not allowed.
- Prior use of 5-alpha-reductase inhibitors is allowed; however, it must be stopped ≥
30 days prior to the pre-registration PSA measure for determining enrollment
eligibility.
- Prior testosterone replacement therapy is allowed; however, any replacement therapy
must be stopped for at least 1 year prior to registration.
- Severe, active co-morbidity defined as follows:
- Current/uncontrolled angina or arrhythmias
- New York Heart Association Functional Classification II-IV (Note: 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.)
- History of any condition that in the opinion of the investigator, would
preclude participation in this study
- Patients with significant obstructive urinary symptoms that are suspected to be
secondary to prostate cancer and/or benign prostatic hypertrophy.
- Disabilities that prevent performing moderate intensity exercise test with exercise
(treadmill) stress test and muscle function tests (walking/gait assessments and grip
strength).
- Patients unable to tolerate MRI (e.g. claustrophobia), has contraindications to MRI
(e.g. metals and implants incompatible with MRI), body habitus preventing MRI
scanning, or allergy to gadolinium-based contrast.
- Significant uncontrolled gastrointestinal (e.g. Crohn's disease, ulcerative colitis)
or metabolic disease (e.g. diabetes, hyperlipidemia).
- Active inflammatory or immune-related disease treated with steroids or
immunosuppressive agents.
- Inability to swallow oral pills.
- High risk features, which includes any of the following:
- Gleason 8-10 [ISUP grade group 4-5]
- PSA>20
- cT3-4 by digital exam OR gross extra-prostatic extension on imaging
[indeterminate MRI evidence will not count and the patient will be eligible]
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shang-Jui Wang
Phone:
614-366-9306
Email:
Shang-Jui.Wang@osumc.edu
Investigator:
Last name:
Shang-Jui Wang
Email:
Principal Investigator
Start date:
August 12, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Ohio State University Comprehensive Cancer Center
Agency class:
Other
Collaborator:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Myovant Sciences GmbH
Agency class:
Industry
Collaborator:
Agency:
Sumitomo Pharmaceuticals America
Agency class:
Industry
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06330805
http://cancer.osu.edu