Stereotactic Body Radiation Therapy Plus Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy for Treatment of Metastatic, Recurrent Hormone-Sensitive Prostate Cancer, DIVINE Trial

Recurrent Prostate Cancer Clinical Trial

— DIVINE  

Official title:

Dynamic Investigator Initiated Enterprise (DIVINE) in Prostate Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06378866
• Other study ID #: MC230502
• Secondary ID: NCI-2024-0297823
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: April 30, 2029

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: April 30, 2029
• Est. primary completion date: April 30, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Hypersensitivity
• Prostatic Neoplasms
• Recurrence
• Recurrent Prostate Cancer
• Stage IVB Prostate Cancer AJCC v8

Intervention

Drug:
• Abiraterone
Given abiraterone
• Apalutamide
Given apalutamide

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Bone Scan
Undergo bone scan
• Computed Tomography
Undergo CT

Drug:
• Darolutamide
Given darolutamide
• Degarelix
Given degarelix
• Enzalutamide
Given enzalutamide
• Goserelin
Given goserelin
• Histrelin
Given histrelin
• Leuprolide
Given leuprolide

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Other:
• Patient Observation
Undergo watchful waiting

Procedure:
• Positron Emission Tomography
Undergo PET

Drug:
• Prednisone
Given prednisone

Other:
• Questionnaire Administration
Ancillary studies

Drug:
• Relugolix
Given relugolix

Radiation:
• Stereotactic Body Radiation Therapy
Undergo SBRT

Drug:
• Triptorelin
Given triptorelin

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified radiographic progression-free survival (mrPFS)	Modified radiographic progression-free survival (mrPFS) is defined as the time from the date of randomization (enrollment to study) to the date of the first occurrence of either death due to any cause or radiographic progression per prostate cancer working group 3 criteria, which are not addressable by stereotactic body radiation therapy (SBRT). Radiographic progression not addressable by SBRT includes 1) soft tissue lesions measured by response evaluation criteria in solid tumors (RECIST) v1.1 or 2) bone lesions evaluated only on bone scans per 2+2 rule (2 new lesions on the 1st post-treatment scan plus 2 additional new lesions on the subsequent scan with persistence or 2 new lesions compared to 1st post-treatment scan persisting on the follow-up scan). Date of progression is the first scan showing lesions. Radiographic progression disease that can be addressed by SBRT will not be an mrPFS event.	Up to 5 years
Secondary	Overall survival (OS)	Defined as time from the date of randomization (enrolled to study) to the date of death due to any cause.	Up to 5 years
Secondary	Biologic progression-free survival (bPFS)	Defined as time from the date of randomization (enrollment to study) to the date of death due to any cause or biologic progressive disease, whichever occurs first.	Up to 5 years
Secondary	Time to local progression (TLP)	Defined as time from date of randomization (enrollment to study) to the date of the first documented local progression. Local progression includes growth of any existing lesion by 20% or more that persists on a subsequent scan (modified from RECIST 1.1), whether or not these lesions are or can be addressed by radiotherapy.	Up to 5 years
Secondary	Time to distant progression (TDP)	Defined as time from date of randomization (enrollment to study) to the date of the first documented distant progression. Distant progression includes new lesions on imaging, whether or not these lesions are or can be addressed by radiotherapy.	Up to 5 years
Secondary	Adverse event (AE) rate	Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of any type of AE during the protocol defined treatment. AEs will be assessed using common terminology criteria for adverse events (CTCAE) v5.0.	Up to 5 years