Table 1.
Prospective trials and tumor registries currently accruing patients in Europe and in the United States for brain tumours
| Tumor type | NCT number | Allocation | Activation (closed) [year] |
# of patients | Age limit | Hypothesis | Primary endpoint | Total dose (dose per fx) [GyRBE] |
status |
|---|---|---|---|---|---|---|---|---|---|
| Europe (lead) | |||||||||
| All brain tumorsa (Dresden, D) |
02824731 | Non-randomized Phase II |
1997 | 418 | no | rate of chronic 1 year toxicity: 15% lower with protons | Chronic toxicity @ 1 year and QoL | 54-60(27-30) | accruing |
| WHO grade II/WHO grade III and IDH mutated (Essen, D) |
DRKS 00015160 NOA-25 |
prospective, randomized (Photons vs Protons) |
2019 | 80 | ≥18 years | Less impairment of neurocognition after proton therapy when compared to photon radiotherapy | Neurocognition after 3 years | WHO II: 54 Gy (30 × 1,8 Gy) WHO III: 60 Gy (30 × 2 Gy) Or 59,4 Gy (33 × 1,8 Gy) |
accruing |
| United States (lead) | |||||||||
| All brain tumors Washington Uni. School of Medicine |
02559752 | Non-randomized Phase II |
2015 | 80 | 4–21 years | Testing as measured by an acceptance rate of 60% of eligible patients administered PT | Feasibility of obtaining serial computer-based neurocognitive testing for patients administered PT | NR | accruing |
| Craniopharyngioma St Judes Children Hospital |
02792582 | Non-randomized Phase II |
1996 | 140 | ≤21 years | Increase of PFS @ 3 years compared to photon data | PFS @ 3 years | 54 (1.8) | accruing |
| Meningioma (Recurrent) Washington Uni. School of Medicine | 03267836 | Phase Ib | 2018 | 12 | ≥18 years | Proof of concept to demonstrate on-target effect of the PT-ICI | Immunogenicity as measured by changes of CD8+/CD4 + TILs | 20(5) with concomitant Avelumab | accruing |
| Meningioma (non-benign) Mass. General Hospital |
02693990 | Non-randomized Phase I/II |
2016 | 60 | ≥18 years | Dose escalation | Assess Safety and Utility of Increased Dose IMPT (DLT) | Dose escalation 3 × 3 design | accruing |
| Low-grade brain tumours Mass. General Hospital |
03286335 | Observational study | 2018 | 100 | ≥18 years | None (observational) | Tumor control @ 2 years | NR | accruing |
| Vestibular Schwannoma Mass. General Hospital |
01199978 | Observational study | 2010 | 30 | ≥18 years | None (observational) | Incidence of late toxicity @ 2 year | 54(27) | Accruing |
| All brain tumours requiring CSA Mass. General Hospital |
03281889 | Feasibility | 2018 | 20 | 3–18 years | To assess if IMPT is feasible for CSA vertebral body sparing | Rate of G3/4 haematological toxicity < 5% within 3 months | NR | Accruing |
| Recurrent Ependymoma St Judes Children Hospital |
02125786 | Non-Randomised Phase II | 2014 | 99 | 1–21 years | To assess if surgery and fractionated re-irradiation with either proton or photon is effective and safe | PFS and OS @ 3 years | NR | Accruing |
| Glioblastoma NRG Oncology |
02179086 | Randomised Phase II | 2014 | 606 | ≥18 years | Dose escalation with IMRT or PT is better than standard dose photon radiation therapy | OS dose escalation vs standard dose | NR | Accruing |
| IDH mutant Glioma (GII/III) NRG Oncology |
03180502 | Randomised Phase II | 2017 | 120 | ≥18 years | PT will preserve cognition compared with IMRT | Change in cognition (CTB COMP scoreb) up to 10 years | NR | Accruing |
| Medulloblastoma St Judes Children Hospital |
01878617 | Phase II | 2013 | 625 | 3–39 years | Assess clinical and molecular risk directed therapy | PFS @ 2 years, neurocognition @ baseline and 12 weeks | NR | Accruing |
| Brain tumours Mayo |
03055364 | Observational study | 2017 | 160 | ≥4 years | None (observational) | Cognitive performance change (CogState) within 12 months of radiotherapy | NR | Accruing |
| Meningioma (G II) NRG Oncology |
03180268 | Randomised Phase III | 2017 | 148 | ≥18 years | Observation vs adjuvant RT in the completely resected setting | PFS up to 10 years | 59.4 (1.8) | Accruing |
| Leptomeningeal metastases MSKCC |
03520504 | Phase I | 2018 | 26 | ≥10 years | Identification of safe and effective dose for PT in leptomeningeal metastases | Number of patients with DLT | 30 (3) or 25 (2.5) CSA | Accruing |
| Patient Registries | |||||||||
| All tumours Washington U |
02040467 | Observational (patient registry) | 2013 | 3200 | no | None (observational) | All treatment data | NR | Accruing |
| All Paediatric tumours Paediatric Consortium Registry (PCCR) |
01696721 | Observational (national patient registry) | 2012 | 5000 | ≤21 years | None (observational) | Establish registry | NR | Accruing |
| All tumours Proton Collaborative Group |
01255748 | Observational (patient registry) | 2010 | 20,000 | All | None (observational) | Establish registry and track outcomes | NR | Accruing |
CSA, Craniospinal axis; DLT, dose-limiting toxicity; IMPT, intensity-modulated proton therapy; IMRT, intensity-modulated photon radiotherapy; NCT: NCI/Clinical Trials.NR, not reported; OS, Overall Survival; PFS, progression-free survival; QoL, quality of life; RT, radiotherapy; TIL, tumour infiltrating lymphocytes; fx, proton therapy dose per fraction.
a
Upfront radiotherapy or re-irradition 30 Gy/RBE in 5 Gy RBE per fraction or 36 Gy/RBE in 2 Gy RBE per fraction.
b
Clinical Trial Battery Composite score (calculated from the Hopkins Verbal Learning Test Revised [HVLT-R]) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Controlled Oral Word Association (COWA) test, Trail Making Test (TMT) part A and part B.