Table 2.
List of completed and ongoing consortium clinical trials for pLGG using targeted therapy.
| Consortium | Phase; NCT # |
Targeted therapy; type of pLGG | Status | Design/Primary Objective(s) | Results |
|---|---|---|---|---|---|
| COG ACNS1831 | III; NCT03871257 |
Selumetinib vs. Carboplatin/ Vincristine for newly diagnosed NF1-associated pLGG |
Ongoing | RCT; primary objectives are to characterize event-free survival and determine number of participants with visual acuity improvement | - |
| COG ACNS1833 | III; NCT04166409 |
Selumetinib vs. Carboplatin/ Vincristine for newly diagnosed non-NF1 pLGG |
Ongoing | RCT; primary objective is to characterize event-free survival | - |
| COG ACNS1931 | III; NCT04576117 |
selumetinib vs. selumetinib/vinblastine for relapsed pLGG | Ongoing | RCT; primary objectives are to determine MTD/RP2D and event-free survival | |
| NFCTC RAD001 [49] | II; NCT01158651 | Everolimus for relapsed NF1-associated pLGG | Completed | One-stage design; primary objective is to assess best response of progressive LGG in previously treated individuals with NF1. | 23 pts (median age 9.4 y); 1 pt removed from study due to development of MPNST. 15/22 (68%) pts had response (1 CR, 2 PR, 12 SD); 10/15 had no progression after median follow-up of 33 months. All pts were alive. |
| NFCTC MEK162 |
I/II; NCT02285439 | MEK162 for pLGG and other Ras/Raf/MAP pathway activated tumors | Ongoing | One-stage design; primary objective of phase I are to determine MTD, and of phase II: to determine the response rate | - |
| PBTC-029B [45] | I/II; NCT01089101 |
Selumetinib for relapsed pLGG | Completed | One-stage design; primary objectives of phase I are RP2D and MTD, and of phase II is objective response (complete response + partial response) rate sustained for 8 weeks | 25 pts; 6 pts w/ PR, 14 pts w/ SD, 5 pts w/ PD; Median treatment courses = 26; 2-y PFS 78% |
| PBTC-055 | I/II; NCT04201457 |
Dabrafenib, trametinib, hydroxychloroquine for relapsed BRAF-mutant pLGG after prior therapy with a RAF and/or MEK inhibitor | Ongoing | One-stage design; primary objectives of phase I are RP2D and MTD, and of phase II is sustained objective response rate defined as “better response” than the best response on prior RAF and/or MEK inhibitor | - |
| PNOC001 [56] | II; NCT01734512 |
Everolimus for relapsed pLGG | Completed | Two-stage design; primary objective is to characterize PFS at 6 Months | 65 pts (median age 9 y); PFS at 6 months 63%; 1 CR, 1 PR, 33 SD, 17 PD |
| PNOC002 [46] | I/II; NCT01748149 | Vemurafenib; relapsed BRAFV600E-mutant pLGG | Completed | One-stage design; primary objectives are to determine the RP2D and DLTs, and characterize objective response rates | I: 19 pts, RP2D 550 mg/m2 twice daily after DLT criteria adjustment for rash; 1 CR, 5 PR, 13 SD |
| PNOC014 [57] | I/II; NCT03429803 | Tovorafenib/DAY101 (TAK-580/MLN2480) for relapsed RAS/RAF/MEK/ERK pathway activated pLGG | Ongoing | One stage design; primary objectives are to determine MTD and RP2D | 9 pts treated at 280, 350, and 420 mg/m2. No DLTs. One patient with grade 3 CPK elevation. Best response: 2 CR, 2 PR, 3 SD, 2 PD with median time to response of 10.5 weeks |
| PNOC021 | I; NCT04485559 |
Trametinib/ Everolimus for relapsed pLGG |
Ongoing | One-stage design; primary objectives are to estimate RP2D, define DLTs, and characterize pharmacokinetic profile of trametinib and everolimus in combination. | - |
| PNOC026 | II; NCT04775485 |
Tovorafenib/DAY101 (TAK-580/MLN2480) for BRAF-altered relapsed pLGG | Ongoing | One-stage design; primary objectives are to define overall response rate by RANO and RECIST v1.1 criteria and characterize safety and tolerability | - |
| POETIC [58] | II; NCT00782626 |
Everolimus for relapsed pLGG | Completed | One-stage design; primary objective is to determine if treatment demonstrated a response rate ≥25% | 23 pts (median age 9.2 y); By week 48, response rate of 52% - 2 pts w/ PR, 10 w/ SD; median FU 1.8 years, 2-y PFS 39%, 2-y OS 93% |
CR, complete response; DLT, dose-limiting toxicity; FU, follow-up; m, months; MPNST, malignant peripheral nerve sheath tumor; MTD, maximum tolerated dose; NFCTC, Neurofibromatosis Clinical Trials Consortium; OS, overall survival; PBTC, Pediatric Brain Tumor Consortium; PFS, progression-free survival; PNOC, Pacific Pediatric Neuro-Oncology Consortium; POETIC, Pediatric Oncology Experimental Therapeutics Investigators' Consortium; PR, partial response; RCT, randomized controlled trial; RP2D, recommended phase 2 dose; SD, stable disease; w/, with; y, years