Combining radiation therapy with hormone treatments for advanced prostate cancer

MC230502 Dynamic Investigator Initiated Enterprise (DIVINE) in Prostate Cancer

This study is testing if combining a specific type of radiation therapy with hormone treatments can help men with advanced prostate cancer live longer and feel better compared to just using radiation alone.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 532 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Mayo Clinic (other)
• Drugs / interventions: Chemotherapy, radiation, prednisone
• Locations: 3 sites (Phoenix, Arizona and 2 other locations)
• Trial ID: NCT06378866 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effects of stereotactic body radiation therapy (SBRT) combined with androgen receptor pathway inhibitors (ARPI) and androgen deprivation therapy (ADT) in patients with recurrent hormone-sensitive prostate cancer that has metastasized. The study aims to compare modified radiographic progression-free survival and overall survival between two treatment groups: one receiving SBRT with ADT/ARPI and the other receiving SBRT alone. Patients will be monitored for various outcomes, including biochemical progression-free survival and toxicity profiles, to assess the effectiveness and safety of the treatment regimen.

Who should consider this trial

Good fit: Ideal candidates are men aged 18 and older with recurrent hormone-sensitive prostate cancer and five or fewer metastases.

Not a fit: Patients with more than five metastases or those with castration-resistant prostate cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve survival rates and quality of life for patients with advanced prostate cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of radiation and hormone therapies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Disease characteristics:

  * DEVIATE (Groups A and B only):

    * 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
  * BRIO (Gropus C \& D only):

    * Prostate-specific antigen (PSA) between 0.2 and 1.5 ng/mL with PSA above 0.2 on at least two consecutive measurements at least 5 days apart
    * No local or metastatic recurrence apparent on advanced molecular imaging
    * Serum testosterone \> 100 ng/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: Curatively treated non-melanotic skin cancer or papillary thyroid cancer
  * 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 prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Where this trial is running

Phoenix, Arizona and 2 other locations

• Mayo Clinic in Arizona — Phoenix, Arizona, United States (RECRUITING)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (RECRUITING)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (RECRUITING)

Study contacts

• Principal investigator: Jacob J. Orme, MD, PhD — Mayo Clinic in Rochester
• Study coordinator: Clinical Trials Referral Office

Conditions: Recurrent Castration-Sensitive Prostate Carcinoma, Recurrent Prostate Cancer, Castration-resistant Prostate Cancer, Biochemically Recurrent Prostate Carcinoma