Nodal Oligorecurrent Prostate Cancer, Oligometastatic Cancer, Oligo-metastatic Prostate Carcinoma, Prostate Cancer
Conditions
Keywords
Single-fraction SBRT, Nodal oligorecurrent prostate cancer, MR-guided SBRT, MR-Linac, Stereotactic body radiotherapy, Stereotactic ablative radiotherapy, Single-fraction radiotherapy, Oligometastasis / oligorecurrence, Metastasis-directed therapy, PSMA-PET/CT, Lymph node metastasis
Brief summary
This single-arm phase 2 trial investigates whether a single high-dose radiotherapy treatment can safely treat men whose prostate cancer has come back in a small number of lymph nodes in the pelvis or abdomen after curative treatment. Participants receive one fraction of 24 Gy delivered with MR-guided stereotactic body radiotherapy (SBRT), which uses MRI to visualise the tumour and surrounding organs during treatment. The main goal is to assess safety (severe side effects). The trial also evaluates local tumour control, longer-term side effects, time until hormone (androgen deprivation) therapy is needed, survival, and quality of life. The trial aims to enrol 48 patients.
Detailed description
PINPOINT is a prospective, investigator-initiated, single-centre, single-arm phase 2 trial of single-fraction MR-guided SBRT in patients with nodal oligorecurrent prostate cancer. Eligible men have PSMA-PET/CT-verified nodal relapse in the pelvis or abdomen following curatively intended local treatment. All patients are simulated with MRI in treatment position and treated with 24 Gy in 1 fraction to the gross tumour volume (GTV) using inverse-planned step-and-shoot IMRT on an MR-linac. No CTV margin is added (CTV = GTV); PTV margins account for motion and set-up uncertainty. Normal-tissue constraints are prioritised over target coverage. The primary endpoint is cumulative CTCAE v5 grade ≥4 treatment-related toxicity within 6 months. Sample size follows a Simon two-stage design (H0: grade 4-5 TRAE rate 15%; H1: 4%; one-sided α = 5%, power 80%), with an interim analysis after 6-month follow-up of the first 16 patients and a total of 48 patients. Follow-up continues for 5 years. Toxicity (CTCAE v5), quality of life (EQ-5D-5L, EORTC QLQ-C30) and patient-reported outcomes (PRO-CTCAE) are collected at baseline and through follow-up; PSA and PSMA-PET/CT (on rising PSA) follow standard of care.
Interventions
RADIATIONSingle-fraction SBRT
Participants will receive 24 Gy in 1 fraction to a lymph node.
Sponsors
Odense University Hospital
Danish Cancer Society
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Signed informed consent * Histologically proven initial diagnosis of adenocarcinoma of the prostate * ECOG performance status 0-2 * Biochemical recurrence after curatively intended local treatment (radical prostatectomy and/or radiotherapy), with PSMA-PET/CT-verified nodal relapse in the pelvis or abdomen * Any additional sites of disease beyond the protocol-specified target lymph nodes must be considered suitable for ablative treatment * Life expectancy \> 6 months * Lymph node size ≤ 2 cm
Exclusion criteria
* Medical contraindications to MRI * Inability to tolerate the physical set-up required for SABR * Overlap between prior radiation fields and the current target area leading to high risk of clinically significant normal-tissue injury * Contraindications to pelvic radiotherapy (chronic pelvic inflammatory bowel disease) * Uncontrolled intercurrent illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with cumulative CTCAE v5.0 grade ≥4 treatment-related adverse events | Within 6 months after completion of radiotherapy | The NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 measures side-effects. Possible scores range from 0-5, with higher scores indicating a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with late adverse events (CTCAE v5.0) | 1, 1,5, 2, 3 and 5 years | The NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 measures side-effect. Possible scores range from 0-5, with higher scores indicating a worse outcome. |
| Percentage of participants free from local progression (PSMA-PET/CT-verified), estimated by time-to-event analysis | From radiotherapy until local progression or last follow-up, up to 5 years | Defined as freedom from PSMA-verified relapse within the treated area. In the case of significant increase in PSA, a PSMA will be performed as to local guidelines. Local control will be evaluated at a lesion level, lesion by lesion. Within the treated area is defined as within or adjacent to the planning target volume (PTV). |
| Median clinical progression-free survival | From radiotherapy up to 5 years | Defined as time from inclusion to any new node or distant metastases recurrence. |
| Median time to initiation of palliative ADT (ADT-free survival) | From inclusion up to 5 years | ADT-free survival is defined as the time from trial randomization to start of hormonal treatment |
| Number of participants with acute adverse events (CTCAE v5.0), by maximum grade | Within 6 months after radiotherapy | The NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 measures side-effects. Possible scores range from 0-5, with higher scores indicating a worse outcome. |
| Median overall survival | From inclusion up to 5 years | Overall survival is defined as time form inclusion to death from any cause |
| Mean change from baseline in EQ-5D-5L index (utility) score | Baseline, 2 weeks, 3,6 and 12 months | The EQ-5D-5L is a standardized, validated generic instrument for health-related quality of life. It comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five response levels. Responses are converted to a single summary index (utility) score using a country-specific (Danish) value set, anchored at 1 = full health and 0 = death, with negative values possible for health states considered worse than death; higher scores indicate better health-related quality of life. The outcome is reported as the mean change from baseline in the EQ-5D-5L index score at each assessment time point. |
| Mean change from baseline in EORTC QLQ-C30 Global Health Status / QoL scale score | Baseline, 2 weeks, 3, 6 and 12 months | The EORTC QLQ-C30 (version 3.0) is a validated cancer-specific questionnaire for assessing health-related quality of life in clinical trials. It contains 30 items comprising a global health status / quality of life scale, five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), and several single-item symptom and financial-impact measures. Raw scores are linearly transformed to a 0-100 scale according to the EORTC scoring manual; for the global health status / QoL scale a higher score indicates better quality of life. This outcome is reported as the mean change from baseline in the global health status / QoL scale score at each assessment time point. |
| Number of participants reporting symptomatic adverse events as assessed by PRO-CTCAE | Baseline, 2 weeks, 3,6 and 12 months | PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) is a validated patient-reported measurement system developed by the NCI to capture symptomatic toxicity in cancer clinical trials. A predefined subset of PRO-CTCAE items is used in this trial. Each symptom is rated by the patient over the prior 7 days across the applicable attributes - frequency (never to almost constantly), severity (none to very severe), and/or interference with usual or daily activities (not at all to very much) - each on a 5-point ordinal scale (scored 0-4). The outcome is reported as the number of participants in each response category per item and attribute at each assessment time point. |
Countries
Denmark
Contacts
CONTACTKristine S Nielsen, MD
CONTACTTine Schytte, Professor
Outcome results
None listed