Phase 2 randomized study of high-risk metachronous oligometastatic prostate cancer with high-risk mutations treated with metastasis-directed therapy and niraparib/abiraterone acetate plus prednisone (KNIGHTS) trial.
Bibliographic record
Abstract
TPS283 Background: Some patients with oligometastases may have the potential for long-term disease-free survival with just aggressive local therapy as shown by randomized trials for total consolidation of macroscopic metastases using metastasis-directed therapy (MDT). Long-term outcomes of pooled STOMP and ORIOLE trials in oligorecurrent metastatic castration-sensitive prostate cancer (omCSPC) demonstrated MDT improved progression free survival. However, men with high-risk mutations, including pathogenic alterations in ATM , BRCA1/2 , Rb1 , and TP53 , did poorly. Additional data suggests men with metastatic castration-resistant prostate cancer and similar mutations are sensitive to PARP inhibition (PARPi) with niraparib. We are launching a first-in-man biomarker-driven trial in omCSPC patients with high-risk mutations to evaluate the efficacy of MDT + androgen deprivation therapy (ADT) versus MDT + ADT + niraparib/abiraterone acetate plus prednisone (nira/AAP). Methods: This study is a multi-site, non-blinded, randomized phase II trial in patients with omCSPC. Men with histologically confirmed (at any site) omCSPC (≤3 metastases on standard imaging or ≤5 on Axumin/Choline/PSMA-PET/CT) and germ-line/somatic high-risk mutations ( TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH ) will be randomized (1:1) to MDT + 6- months ADT versus MDT + 6-months ADT + 6-months nira/AAP. A range of MDT radiation fractionation regimens are permitted. Subjects who meet eligibility criteria and qualify for enrollment will be stratified according to: (i) institution; (ii) conventional/enhanced imaging, (iii) PSADT <6-months, (iv) initial surgery/radiation, and (v) BRCA1/2 status. This study has been IRB approved (NCT06212583). We assume an accrual time of 24 months, with 18 months of additional follow-up time, and will randomize a total of 88 patients (44 patients in each arm). The primary endpoint will be to assess frequency of PSA failure (> 0.2 ng/mL post primary surgery or nadir + 2 post definitive radiation) with testosterone >100 ng/dl at 18-months after randomization (powered for 20% improvement over control arm by Fisher’s exact test). Secondary endpoints will include toxicity, health-related quality of life (HRQoL), time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival, and duration of response. Discovery correlatives associated with clinical outcome will be assessed by collection of including, but not limited to, cell free DNA, circulating-tumor cells, immunologic biomarkers, microbiota and radiomics. Clinical trial information: NCT06212583 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".