A Randomized Open Label Phase II Trial of FDG-PET-Guided Metastasis Directed Therapy in Patients With Metastatic Hormone Sensitive Prostate Cancer: PRTY Trial: PET- Guided Radiotherapy Consolidation
This phase II trial compares the effect of FDG-positron emission tomography (PET)-guided metastasis directed radiation therapy (MDRT) in combination with standard treatments to standard treatments alone in treating patients with prostate cancer that is sensitive to androgen-deprivation therapy (ADT) and has spread from where it first started (primary site) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer death among men in the United States, despite the approval of several life-prolonging treatments by the Food and Drug Administration. However, over the past 10 years, there have been significant improvements in prolonging the lives of those with metastatic hormone sensitive prostate cancer, specifically by adding treatments to standard therapy, such as ADT. More recently, trials have demonstrated a benefit of using radiotherapy (high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors) to delay the progression of cancer and prolong life for patients with metastatic disease. Imaging scans with FDG-PET may be able to identify cancer sites that remain active despite standard treatment. Giving MDRT plus standard treatment to patients with FDG-PET-identified cancer sites may work better than standard treatment alone in treating metastatic hormone sensitive prostate cancer.
• Patients must have metastatic prostate cancer on conventional imaging (CT scan, MRI, and/or bone scan).
‣ Note; Patients who had metastatic disease on conventional imaging prior to beginning ADT, but which has now resolved, are still eligible if they meet remaining eligibility criteria
• Patients must be ≥ 18 years of age at the time of informed consent.
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
• Planned treatment requirements:
‣ Cohort 1
∙ Patients must have mHSPC and be planning therapy with cytotoxic therapy, with or without an androgen receptor (AR) pathway inhibitor (ARPI), to be eligible for Cohort 1. Patients may also enroll if they are currently receiving or have completed cytotoxic therapy, if they are within 26 weeks +/- 4 weeks (30 weeks) of starting cytotoxic therapy and 26 weeks +/- 26 weeks (one year) of starting ADT.
• Note:
‣ Typically cytotoxic therapy means docetaxel. Patients planning other cytotoxic therapy (e.g. cabazitaxel) should discuss this with the study principal investigator (PI).
⁃ If a patient registers as part of cohort 1 but ends up not receiving any cytotoxic therapy, the patient may be switched to cohort 2. This must be discussed with the study PI. If the patient received at least one cycle of cytotoxic therapy, they would remain in cohort 1.
⁃ Patients will continue their standard of care treatment while on study (plus MDRT if they are on Arm 1A). Change in standard of care therapy will be allowed for toxicity or for de-escalation, and the patient will remain on study. Change in therapy for progression is considered a progression event.
⁃ Cohort 2
∙ Patients must have mHSPC and be planning therapy with androgen deprivation therapy (ADT), with or without an ARPI, and not planning cytotoxic therapy, to be eligible for Cohort 2. Patients may also enroll if they are within 26 weeks +/- 4 weeks (30 weeks) of starting an AR pathway inhibitor and 26 weeks +/- 26 weeks (one year) of starting ADT.
• Note:
‣ If patients register as part of cohort 2 but end up receiving one or more cycles of cytotoxic therapy, they may be switched to cohort 1. This must be discussed with the study PI.
⁃ Patients will continue their standard of care treatment while on study (plus MDRT if they are on Arm 2A). If they switch therapy because of progression, they will be considered to have progressed.
⁃ Patients can be enrolled anytime within the initial \
∙ 6 month standard of care time period, though early enrollment is preferred. Screening can take place prior to starting standard of care (SOC) therapy or during standard of care therapy, as long as they are within 30 weeks of starting therapy.
• Leukocytes (WBC) ≥ 2,500/mcL (growth factor use allowed) (obtained prior to registration).
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (growth factor use allowed) (obtained prior to registration).
• Platelets (PLT) ≥ 80,000/mcL (transfusions allowed) (obtained prior to registration).
• Patient must be able to lie flat and still for approximately 15-20 minutes AND able to tolerate FDG-PET/CT radiographical imaging and radiation treatment planning and delivery.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the endpoints for this study, in the opinion of the treating investigator, are eligible.
‣ Note; Patients are ineligible if another known malignancy makes it difficult to interpret if FDG-avid lesions represent prostate cancer, or if the malignancy is expected to interfere with patients receiving standard therapy for prostate cancer for 2 years from study enrollment.
• Patients must have a life expectancy of at least 6 months, in the opinion of the treating investigator.
• Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration.
‣ Note: Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.