None listed
Conditions
Brief summary
The POCAHONTAS study is aiming to evaluate the optimal timing of stereotactic ablative radiotherapy (SABR) in combination with standard systemic therapy for men with metastatic hormone-sensitive prostate cancer with four to ten metastases. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have histologically confirmed prostate cancer with metastatic disease detected on PSMA-PET/CT imaging within eight weeks prior to randomisation, have between four and ten metastatic lesions identified, have hormone-sensitive or hormone-naïve disease, an ECOG performance status of 0–1, and all sites of disease are amenable to treatment with SABR. Study details All participants receive standard-of-care systemic therapy, including androgen deprivation therapy with or without additional agents. Participants will then be randomly allocated (by chance) to one of two groups to receive either (1) immediate upfront SABR to all metastatic lesions or (2) delayed SABR (six months post-randomisation) to residual disease following initial systemic therapy. Participants will undergo PSMA-PET/CT imaging, blood tests and complete questionnaires during regular three-monthly follow-up visits for the first two years and six-monthly thereafter, for up to approximately three years post-randomisation, to determine outcomes including three-year castration-resistant prostate cancer–free survival, change in systemic therapy, overall survival, incidence of adverse events and quality of life. It is hoped that this research will help define the most effective timing of SABR in combination with systemic therapy, with the potential to improve long-term outcomes and delay disease progression for men with advanced prostate cancer.
Interventions
Participants randomised to Arm A will receive upfront stereotactic ablative radiotherapy (SABR) to all PSMA-PET–avid metastatic lesions (up to 10 sites). SABR dose and fractionation will be individualised according to lesion characteristics, proximity to organs at risk, and patient factors. Permitted regimens range from 20 Gy in a single fraction to 35–50 Gy in 5 fractions, with different lesions permitted to receive different dose-fractionation schedules.
SABR will be delivered by specialist ra
Participants randomised to Arm A will receive upfront stereotactic ablative radiotherapy (SABR) to all PSMA-PET–avid metastatic lesions (up to 10 sites). SABR dose and fractionation will be individualised according to lesion characteristics, proximity to organs at risk, and patient factors. Permitted regimens range from 20 Gy in a single fraction to 35–50 Gy in 5 fractions, with different lesions permitted to receive different dose-fractionation schedules. SABR will be delivered by specialist radiation oncology teams over a short treatment course of 1–5 fractions, typically administered on alternate days for multi-fraction regimens. All SABR treatment must commence within 4 weeks of randomisation and is expected to be completed within approximately 1–2 weeks from treatment initiation, depending on the fractionation schedule and number of lesions treated. In addition to SABR, all participants will receive standard-of-care systemic therapy consisting of androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitor (ARPI), with or without chemotherapy, at the discretion of the treating clinician. Intermittent ADT is not permitted. Systemic therapy is intended to continue long-term in accordance with standard clinical practice and study follow-up requirements. For the purposes of the study, systemic therapy must be administered for a minimum of 6 months following randomisation and may continue for the duration of the participant's involvement in the study, with no protocol-specified maximum duration.
Sponsors
Icon Group
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria: Adult males aged 18 years or older Histologically or cytologically confirmed prostate cancer with metastatic disease (M1) detected on PSMA-PET/CT imaging within 8 weeks prior to randomisation Presence of 4 to 10 metastatic lesions identified on PSMA-PET/CT Hormone-sensitive or hormone-naïve disease (i.e. not castration-resistant) ECOG performance status 0–1 All identified metastatic sites must be considered amenable to safe treatment with stereotactic ablative radiotherapy (SABR) Estimated life expectancy greater than 24 months Willing and able to provide written informed consent Additional eligibility considerations: Prior treatment to metastatic sites is permitted if the site is controlled or requires SABR as per protocol criteria Prior androgen deprivation therapy (ADT) is permitted if completed >24 months prior, or if testosterone has recovered to eugonadal levels before enrolment
Exclusion criteria
Participants will be excluded if they have castration-resistant prostate cancer, more than ten metastatic lesions at baseline, or serious medical conditions that make the safe delivery of stereotactic ablative radiotherapy unsuitable. Exclusion also applies to individuals with brain metastases, leptomeningeal disease, spinal cord compression, or malignant pleural effusion. Patients with tumour histology showing significant sarcomatoid, ductal, spindle cell, or neuroendocrine (small cell) features are not eligible, nor are those with an active malignancy other than prostate cancer, except for adequately treated non-melanoma skin cancer or superficial bladder cancer. Individuals with a prior non-prostate malignancy are excluded unless they have been disease-free for three years following their last treatment. Patients with known radiation sensitivity syndromes or connective tissue disorders that increase the risk from radiotherapy are also excluded.
Outcome results
None listed