Evaluation of TQ-B3234 Capsules in Patients With Symptomatic, Non-Surgical Type 1 Neurofibromatosis-Associated Plexiform Neurofibromas

Browse trials for

• Neurofibroma, Plexiform 66

Study arms

• Experimental
  TQ-B3234 capsules

  TQ-B3234 capsules: 50 mg once daily, one cycle every 4 weeks (28 days)

  Drug: TQ-B3234 capsules

• Placebo comparator
  TQ-B3234 placebo

  TQ-B3234 placebo: 0 mg once daily, one cycle every 4 weeks (28 days)

  Drug: TQ-B3234 placebo

Interventions

• DrugTQ-B3234 capsules

  TQ-B3234 is an antitumor molecular targeted drug, a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor. It primarily inhibits the mitogen-activated protein kinase (MEK) protein (an upstream regulator of the extracellular signal-regulated kinase (ERK) pathway), thereby affecting the mitogen-activated protein kinase (MAPK) pathway and suppressing cell proliferation. MEK inhibitors are recognized to play a significant role in the pathogenesis of plexiform neurofibromas associated with neurofibromatosis type 1.

• DrugTQ-B3234 placebo

  TQ-B3234 placebo without drug substance.

Primary outcomes

1. IRC-Assessed Objective Response Rate (ORR)

   Percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by independent review committee (IRC) per REiNS criteria at the end of Cycle 24.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

Secondary outcomes

1. Investigator-Assessed ORR

   Percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

2. IRC/Investigator-Assessed DOR

   Duration of response (DOR), defined as the time from first documented confirmed objective response to disease progression or death from any cause (whichever occurs first), as determined by IRC/investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

3. IRC/Investigator-Assessed disease control rate (DCR)

   Percentage of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) as determined by IRC/investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

4. IRC/Investigator-Assessed progression-free survival (PFS )

   Time from randomization to first disease progression or death from any cause (whichever occurs first), as determined by IRC/investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

5. IRC/Investigator-Assessed TTP

   Time from randomization to first disease progression (TTP), as assessed by IRC/investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

6. IRC/Investigator-Assessed time to response (TTR)

   Time from randomization to first objective response, as determined by IRC/investigators per REiNS criteria.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

7. Tumor response in subject

   Difference in the best percentage change from baseline in target PN volume between groups, as assessed by IRC/investigators.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

8. Number of subjects with incidence and severity of adverse events (AEs)

   Incidence and severity of adverse events from subject enrollment to the end of cycle 24.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

9. Patient-reported outcomes

   Patient self-assessment results from subject enrollment to the end of cycle 24.

   Time frame: From subject enrollment to the end of cycle 24 (each cycle is 28 days)

10. Peak concentration (Cmax)

    Maximum plasma drug concentration

    Time frame: 2 hours after administration

11. Plasma concentration at steady state (Ctrough, SS)

    The pre-dose concentration observed when the drug has reached steady state with repeated dosing, indicating baseline exposure and accumulation.

    Time frame: Cycle 1 day 28: pre-dose, Cycle 2 day 28 pre-dose, Cycle 3 day 28: pre-dose, Cycle 6 day 28: pre-dose. (each cycle is 28 days)

12. Effects on pain score in subjects

    Questionnaire: Numerical Rating Scale-11 (NRS-11); The line segments below all have numbers from 0 to 10, where 0 means no pain and 10 is the worst pain you can imagine.

    Time frame: From subject enrollment to the end of the 24th cycle (each cycle is 28 days)

13. Effects on pain interference index in subjects

    Questionnaire: pain interference index; Please answer each one by circling a number from 0 to 6, where 0 means none at all and 6 means completely

    Time frame: From subject enrollment to the end of the 24th cycle (each cycle is 28 days)

14. Effects on subjects' general quality of life

    Questionnaire: Functional Assessment of Cancer Therapy - General (FACT-G); the scores from all items across its four domains are summed to obtain a total score, which ranges from 0 to 108 points.

    Time frame: From subject enrollment to the end of the 24th cycle (each cycle is 28 days)

15. Effects on subjects; disease-specific quality of life

    Questionnaire: PedsQL NF1 Module; It includes an Adult version (\>25 years) and a Young Adult version (18-25 years), with 104 items, respectively.

    Time frame: From subject enrollment to the end of the 24th cycle (each cycle is 28 days)