Trial Title:
Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED)
NCT ID:
NCT06463457
Condition:
Prostate Cancer
Advanced Prostate Cancer
Hormone Sensitive Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Hypersensitivity
Relugolix
Conditions: Keywords:
Hormone-Sensitive Prostate Cancer
Prostate Cancer
Advanced Prostate Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Darolutamide
Description:
Androgen receptor antagonist, tablet taken orally per protocol.
Arm group label:
Cohort 1 Short Pharmacokinetics (PK)
Arm group label:
Cohort 2 Long Pharmacokinetics (PK)
Other name:
ODM-201
Other name:
Bay 1841788
Other name:
C19H19CIN6O2
Intervention type:
Drug
Intervention name:
Relugolix
Description:
Gonadotropin-releasing hormone (GnRH) receptor antagonist, tablet taken orally per
protocol.
Arm group label:
Cohort 1 Short Pharmacokinetics (PK)
Arm group label:
Cohort 2 Long Pharmacokinetics (PK)
Other name:
Orgovyx
Other name:
RVT-601
Other name:
TAK-385
Other name:
1-[4-[1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea
Other name:
C29H27F2N7O5S
Summary:
This research study is being done to determine the rate of testosterone recovery after
completing two years of treatment with the combination of relugolix and darolutamide as
well as to assess the safety of the drugs when administered in combination.
The names of the drugs in this study are:
- Relugolix (a type of gonadotropin-releasing hormone receptor antagonist)
- Darolutamide (a type of androgen receptor antagonist)
Detailed description:
The aim of this single-arm phase 2 study is to assess testosterone recovery after
completion of two years of combination treatment with relugolix and darolutamide and to
describe safety, tolerability and pharmacokinetics of relugolix and darolutamide when
administered in combination. Participants will select enrollment into one of two groups
(Group 1 or Group 2). The purpose of Group 1 is to determine the amount of each drug in
the bloodstream after 2 hours, 4 hours, and 8 hours of treatment, whereas the purpose of
Group 2 is to determine the amount of each drug in the bloodstream after 1 day, 7 days,
and 28 days of treatment.
The US Food and Drug Administration (FDA) has approved relugolix for the treatment of
advanced prostate cancer.
The FDA has approved the combination of darolutamide with docetaxel for initial treatment
of metastatic prostate cancer, that is, cancer that has spread to other parts of the
body. The FDA has also approved darolutamide alone for treatment of non-metastatic
castration-resistant prostate cancer, that is, cancer that has become resistant to
testosterone lowering medications without evidence of spread of the cancer to other parts
of the body that can be detected on Computerized Tomography (CT) or bone scans.
While darolutamide and relugolix can be prescribed together based on the FDA-approved
indications of the individual drugs, this combination has not been approved by the FDA or
formally tested in clinical trials.
The research study procedures include screening for eligibility, study treatment visits,
questionnaires, and blood tests. Electrocardiograms (EKGs) will be performed if felt to
be clinically indicated by the treating physician. Imaging using a Computerized
Tomography (CT) scan, Magnetic Resonance Imaging (MRI) scan, bone scan, and/or
Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) scan is
required before starting study treatment, and will be performed after starting study
treatment when felt to be clinically indicated by the treating physician.
Participants will receive study treatment of relugolix and darolutamide for 2 years and
will be followed for 18 months after the treatment period.
It is expected that about 33 participants will take part in this research study.
Bayer AG, Pfizer, and Sumitomo Pharma America (SMPA), Inc. are funding this research
study. Bayer and SMPA are providing the study drugs darolutamide and relugolix,
respectively.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed prostate cancer.
- Hormone-sensitive prostate cancer (with detectable prostate-specific antigen [PSA] >
0.02 ng/ml, testosterone ≥ lower limit of normal [LLN] per institutional assay)
planned for two years of intensified androgen deprivation therapy per investigator
discretion. This includes the following indications:
- Treatment-naïve high risk lymph node-negative (N0) disease planned for primary
radiation therapy
- Treatment-naïve clinically pelvic lymph node positive (cN+) disease planned for
primary radiation therapy
- Pathologically pelvic lymph node positive (pN+) disease after prostatectomy
planned for salvage radiation therapy
- Regional nodal recurrence after prior local therapy (often in the context of
radiation to lymph nodes)
- Synchronous or metachronous low volume metastatic hormone sensitive prostate
cancer (mHSPC) by Chemohormonal Therapy Versus Androgen Ablation Randomized
Trial for Extensive Disease (CHAARTED) criteria planned for treatment
interruption after 2 years (often in the context of radiation to sites of
disease).
- N.B: While CHAARTED criteria were established based on conventional imaging,
patients who had PSMA PET imaging that would meet criteria for high volume
disease (visceral metastases or ≥ 4 definitive bone metastases with at least
one outside the axial skeleton) are excluded from this study.
- Prior hormonal therapy is permitted in the context of
neoadjuvant/concurrent/adjuvant treatment with prior local therapy or biochemical
recurrence by conventional imaging (for patients enrolling for recurrent rather than
treatment-naïve disease), but patients must have had testosterone recovery to ≥ LLN
at time of enrollment to this trial.
- Age ≥18 years. Children under 18 are excluded from this study as prostate cancer is
a disease of adults.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥70%).
- Participants must meet the following organ and marrow function as defined below:
- leukocytes ≥2500/mcL
- absolute neutrophil count ≥1000/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) unless known or
suspected Gilbert syndrome
- aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 ×
institutional ULN
- glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (based on Cockcroft-Gault
formula, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) refit
formula, OR creatinine clearance based on 24 hour urine collection)
- Human immunodeficiency virus (HIV)-infected participants on effective
anti-retroviral therapy (with no known or predicted drug-drug interactions with
darolutamide and/or relugolix) with undetectable viral load within 6 months are
eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable. If suppressive therapy is indicated, there must be
no known or predicted drug-drug interactions with darolutamide and/or relugolix.
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on
treatment, they are eligible if there are no known or predicted drug-drug
interactions with darolutamide and/or relugolix and they have an undetectable HCV
viral load.
- Participants 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, participants should be class 2B or better.
- Ability to swallow oral medications.
- The effects of darolutamide and/or relugolix on the developing human fetus are
unknown. For this reason and because oral hormonal agents are known to be
teratogenic, participants must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. 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. Participants treated or enrolled on this protocol
must also not donate semen or sperm and agree to use adequate contraception prior to
the study, for the duration of study participation, and 3 months after completion of
darolutamide and relugolix administration.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Participants who received prior systemic therapy for the disease state (high risk
localized, lymph node positive, or low volume mHSPC) for which they are enrolling on
this trial. Prior hormonal therapy is permitted for patients with recurrent disease
after prior therapy.
- Participants who previously experienced any rise in PSA with castrate level
testosterone (< 50 ng/dl).
- Participants who are receiving any other investigational agents for this condition.
- Participants with brain metastases, leptomeningeal disease, or metastases involving
other visceral organs since these patients would be considered to have "high volume"
metastatic disease by CHAARTED criteria.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to relugolix or darolutamide.
- Participants with predicted significant drug-drug interaction with darolutamide
and/or relugolix are ineligible or must be monitored carefully as detailed below:
- Participants receiving combined P-glycoprotein (P-gp) and strong CYP3A inducers
(e.g. apalutamide, carbamazepine, fosphenytoin, phenobarbital, phenytoin,
primidone, rifampin, rifapentine, and St. John's wort) or combined P-gp and
moderate CYP3A4 inducers (e.g. efavirenz, rifabutin) are ineligible.
- Participants receiving combined P-gp and strong CYP3A4 inhibitors (e.g.
ketoconazole, itraconazole, posaconazole, clarithromycin, cobicistat,
cyclosporine, tacrolimus, nelfinavir, ritonavir, lopinavir, saquinivir,
tipranavir) are ineligible to enroll.
- Participants receiving Breast cancer resistance protein (BCRP) substrates (e.g.
glyburide, cimetidine, nitrofurantoin, dipyridamole, sulfasalazine, and
rosuvastatin) are not excluded but participants should be monitored more
frequently for adverse reactions to the BCRP substrate drug, and dose reduction
of the BCRP substrate drug should be considered.
- Participants receiving P-gp inhibitors are not excluded but participants must
be able to dose the P-gp inhibitor at least 6 hours after relugolix dose during
the conduct of the study. Participants unable to dose the P-gp inhibitor at
least 6 hours after relugolix dose, or requiring twice daily or more frequent
dosing of a P-gp inhibitor are ineligible.
- Because the lists of these agents are constantly changing, it is important to
regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the participant will be counseled on
the risk of interactions with other agents, and what to do if new medications
need to be prescribed or if the participant is considering a new
over-the-counter medicine or herbal product.
- Participants with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, or cardiac arrhythmia.
- Participants with psychiatric illness/social situations that would limit compliance
with study requirements.
- Pregnant and nursing women are excluded from this study because they do not develop
prostate cancer.
- Concurrent active malignancy. Patients with non-melanomatous skin cancer,
superficial bladder cancer, cancer not needing active systemic therapy for at least
2 years and would not affect imaging assessments for prostate cancer, cancer for
which the treating investigator deems the subject to be in remission, or any prior
malignancy that was treated with curative intent (no evidence of disease for at
least 3 years) are also permitted to enroll.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Daniel Fein, MD
Phone:
617-667-2100
Email:
dfein@bidmc.harvard.edu
Investigator:
Last name:
Daniel Fein, MD
Email:
Principal Investigator
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Atish Choudhury, MD, PhD
Phone:
617-632-6328
Email:
achoudhury@partners.org
Investigator:
Last name:
Atish Choudhury, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Atish Choudhury, MD, PhD
Phone:
617-632-6328
Email:
atish_choudhury@dfci.harvard.edu
Investigator:
Last name:
Atish Choudhury, MD, PhD
Email:
Principal Investigator
Start date:
November 2024
Completion date:
November 30, 2028
Lead sponsor:
Agency:
Atish Choudhury, MD
Agency class:
Other
Collaborator:
Agency:
Bayer
Agency class:
Industry
Collaborator:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Sumitomo Pharma America, Inc.
Agency class:
Industry
Collaborator:
Agency:
National Comprehensive Cancer Network
Agency class:
Other
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06463457
