Trial Title:
Stereotactic Body Radiation Therapy Plus Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy for Treatment of Metastatic, Recurrent Hormone-Sensitive Prostate Cancer, DIVINE Trial
NCT ID:
NCT06378866
Condition:
Recurrent Castration-Sensitive Prostate Carcinoma
Stage IVB Prostate Cancer AJCC v8
Recurrent Prostate Cancer
Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Hypersensitivity
Recurrence
Prednisone
Cortisone
Leuprolide
Goserelin
Triptorelin Pamoate
Abiraterone Acetate
Tryptophan
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:
Drug
Intervention name:
Abiraterone
Description:
Given abiraterone
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
Abiraterone acetate
Other name:
CB-7598
Other name:
CB7598
Other name:
Zytiga
Intervention type:
Drug
Intervention name:
Apalutamide
Description:
Given apalutamide
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
ARN 509
Other name:
ARN-509
Other name:
ARN509
Other name:
Erleada
Other name:
JNJ 56021927
Other name:
JNJ-56021927
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography (CAT)
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:
Darolutamide
Description:
Given darolutamide
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
Antiandrogen ODM-201
Other name:
BAY 1841788
Other name:
BAY-1841788
Other name:
BAY1841788
Other name:
Nubeqa
Other name:
ODM 201
Other name:
ODM-201
Intervention type:
Drug
Intervention name:
Degarelix
Description:
Given degarelix
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
ASP3550
Other name:
FE200486
Other name:
Firmagon
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
Given enzalutamide
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
ASP9785
Other name:
MDV3100
Other name:
Xtandi
Intervention type:
Drug
Intervention name:
Goserelin
Description:
Given goserelin
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
ICI-118630
Intervention type:
Drug
Intervention name:
Histrelin
Description:
Given histrelin
Arm group label:
Group A (SBRT, APRI, ADT)
Intervention type:
Drug
Intervention name:
Leuprolide
Description:
Given leuprolide
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
Leuprorelin
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
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:
Nuclear Magnetic Resonance (NMR) Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging (NMRI)
Other name:
sMRI
Other name:
Structural MRI (sMRI)
Other name:
NMR Imaging
Intervention type:
Other
Intervention name:
Patient Observation
Description:
Undergo watchful waiting
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
Active Surveillance
Other name:
deferred therapy
Other name:
expectant management
Other name:
Observation
Other name:
Watchful Waiting
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography (PET)
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:
Drug
Intervention name:
Prednisone
Description:
Given prednisone
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
.delta.1-Cortisone
Other name:
1, 2-Dehydrocortisone
Other name:
Adasone
Other name:
Cortancyl
Other name:
Dacortin
Other name:
DeCortin
Other name:
Decortisyl
Other name:
Decorton
Other name:
Delta 1-Cortisone
Other name:
Delta-Dome
Other name:
Deltacortene
Other name:
Deltacortisone
Other name:
Deltadehydrocortisone
Other name:
Deltasone
Other name:
Deltison
Other name:
Deltra
Other name:
Econosone
Other name:
Lisacort
Other name:
Meprosona-F
Other name:
Metacortandracin
Other name:
Meticorten
Other name:
Ofisolona
Other name:
Orasone
Other name:
Panafcort
Other name:
Panasol-S
Other name:
Paracort
Other name:
Perrigo Prednisone
Other name:
PRED
Other name:
Predicor
Other name:
Predicorten
Other name:
Prednicen-M
Other name:
Prednicort
Other name:
Prednidib
Other name:
Prednilonga
Other name:
Predniment
Other name:
Prednisone Intensol
Other name:
Prednisonum
Other name:
Prednitone
Other name:
Promifen
Other name:
Rayos
Other name:
Servisone
Other name:
SK-Prednisone
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Intervention type:
Drug
Intervention name:
Relugolix
Description:
Given relugolix
Arm group label:
Group A (SBRT, APRI, ADT)
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
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy
Description:
Undergo SBRT
Arm group label:
Group A (SBRT, APRI, ADT)
Arm group label:
Group B (SBRT, watchful waiting)
Other name:
SABR
Other name:
SBRT
Other name:
Stereotactic Ablative Body Radiation (SABR)
Other name:
Stereotactic Ablative Body Radiation Therapy
Intervention type:
Drug
Intervention name:
Triptorelin
Description:
Given triptorelin
Arm group label:
Group A (SBRT, APRI, ADT)
Other name:
6-D-Tryptophan-LH-RH
Other name:
6-D-Tryptophanluteinizing Hormone-releasing Factor
Other name:
AY-25650
Other name:
AY25650
Other name:
CL-118,532
Other name:
CL118532
Other name:
Detryptoreline
Summary:
This phase II trial studies the effects of stereotactic body radiation therapy (SBRT) and
the timing of treatment with androgen receptor pathway inhibitor (ARPI) plus androgen
deprivation therapy (ADT) in treating patients with hormone sensitive prostate cancer
that has spread from where it first started to other places in the body (metastatic), and
that has come back after a period of improvement (recurrent). SBRT is a type of external
radiation therapy that uses special equipment to position a patient and precisely deliver
radiation to tumors in the body (except the brain). The total dose of radiation is
divided into smaller doses given over several days. This type of radiation therapy helps
spare normal tissue. Androgen can cause the growth of prostate cells. ADT lowers the
amount of androgen made by the body. This may help stop the growth of tumor cells that
need androgen to grow. Androgen receptor pathway inhibitors work by blocking the effects
of androgen to stop the growth and spread of tumor cells. Giving SBRT alone with watchful
waiting may be as effective in treating prostate cancer as giving SBRT together with ARPI
and ADT.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate and compare modified radiographic progression-free survival (mrPFS) in
patients with metachronous recurrent oligometastatic prostate cancer treated with SBRT
and 6 months ADT/ARPI followed by watchful wait (Group A) versus SBRT followed by
watchful wait (Group B).
SECONDARY OBJECTIVES:
I. To evaluate and compare overall survival (OS) between two treatment groups. II. To
evaluate and compare biochemical progression-free survival (bPFS) between two treatment
groups.
III. To evaluate and compare time to local progression between two treatment groups.
IV. To evaluate and compare time to distant progression between two treatment groups.
V. To evaluate the toxicity profile of 6 months of ADT/ARPI as assessed per National
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
TERTIARY OBJECTIVES:
I. To evaluate and compare castration-resistant prostate cancer (CRPC)-free survival
between two treatment groups NOTE: CRPC-free survival: radiographic progression-free
survival with castrate-level testosterone (< 50ng/mL).
II. Determine the efficacy of extracellular vesicles (EVs) as a minimal residual disease
(MRD) marker.
III. Determine the efficacy of EVs as an early indicator of disease relapse. IV.
Characterize duration of response. V. Determine whether early ADT and ARPI hasten CRPC.
VI. Determine how circulating tumor deoxyribonucleic acid (ctDNA) compares as a biomarker
to EVs.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP A: Patients undergo SBRT and receive ARPI (abiraterone and prednisone, apalutamide,
darolutamide, or enzalutamide) and ADT (leuprolide, triptorelin, histrelin, goserelin,
degarelix, or relugolix). Cycles repeat every 4 months (16 weeks) for up to 6 months in
the absence of disease progression or unacceptable toxicity. Patients then undergo
watchful waiting thereafter until disease progression.
GROUP B: Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16
weeks) in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection and positron emission tomography
(PET), computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.
Upon completion of study interventions patients are followed up every 6 months for up to
5 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years
- The following disease characteristics:
- Clinical confirmation of metachronous (metastatic) recurrent hormone-sensitive
prostate cancer
- Five (5) or fewer metastases with at least one metastasis beyond the pelvis on
advanced molecular and/or conventional imaging
- Serum testosterone > 100ng/dL
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
- Hemoglobin ≥ 8.0 g/dL (obtained ≤ 15 days prior to registration)
- Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to
registration)
- Platelet count ≥ 80,000/mm^3 (obtained ≤ 15 days prior to registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x upper limit of
normal (ULN) ( ≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days
prior to registration)
- Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula
(obtained ≤ 15 days prior to registration)
- Provide written informed consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willingness to provide mandatory blood specimens for correlative research
- Willingness to provide tissue specimens for correlative research
- Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)
Exclusion Criteria:
- Any of the following because this study involves an investigational agent, the
genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and
newborn are unknown
- Pregnant persons
- Nursing persons
- Persons of childbearing potential or able to father a child who are unwilling
to employ adequate contraception
- Prior metastasis-directed therapy
- Any of the following prior therapies:
- Surgery ≤ 3 weeks prior to registration
- Chemotherapy for prostate cancer at any time
- Androgen receptor pathway inhibitor such as abiraterone, apalutamide,
darolutamide, or enzalutamide in the last 2 years
- Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- Ongoing or active infection
- Psychiatric illness/social situations
- Dyspnea at rest due to complications of advanced malignancy or other disease
that requires continuous oxygen therapy
- Any other conditions that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment
for prostate cancer.
- Failure to recover from acute, reversible effects of prior therapy regardless of
interval since last treatment EXCEPTION: Grade 1 peripheral (sensory) neuropathy
that has been stable for at least 3 months since completion of prior treatment
- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Or psychiatric illness/social situations that would limit compliance with study
requirements
- Receiving any other investigational agent which would be considered as a treatment
for the primary neoplasm
- Other active malignancy ≤ 3 years prior to registration
- EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
- NOTE: If there is a history of prior malignancy, they must not be receiving
other specific treatment such as chemotherapy or antihormonal therapy for their
cancer
- History of myocardial infarction ≤ 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Jacob J. Orme, M.D., Ph.D.
Email:
Principal Investigator
Start date:
June 3, 2024
Completion date:
May 31, 2029
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06378866
https://www.mayo.edu/research/clinical-trials
