Plexiform Neurofibroma
Conditions
Brief summary
This study aims to demonstrate that in subjects with symptomatic, inoperable plexiform neurofibromas associated with neurofibromatosis type 1, TQ-B3234 capsules significantly improve the objective response rate at Week 24 compared to 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.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject voluntarily joins this study, signs the informed consent form, and demonstrates good compliance. * Age ≥18 years (calculated from the date of signing the informed consent form). * Diagnosis of symptomatic, non-resectable neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) requiring systemic therapy per investigator judgment. * At least one measurable lesion with a dimension ≥3 cm. * There should be no significant changes in the use of chronic neuropathic pain medications within 28 days prior to study enrollment. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Laboratory tests meet the protocol criteria. * Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion. A negative serum pregnancy test must be documented within 7 days prior to study enrollment. Men must agree to use effective contraception during the study and for 6 months after study completion.
Exclusion criteria
* Confirmed or suspected malignant glioma or malignant peripheral nerve sheath tumor (MPNST) (excluding low-grade glioma, optic nerve glioma not requiring systemic therapy or radiotherapy); histological confirmation may be required. * History of or concurrent other malignancies within 5 years prior to first dosing. * Multiple factors affecting oral drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction, major bowel resection). * Adverse reactions from prior anti-tumor therapy not recovered to NCI CTCAE v6.0 grade ≤1, except grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy. * Major surgery, significant traumatic injury, or planned major surgery during the study within 4 weeks prior to first dosing; or presence of long-term non-healed wounds or fractures. * History of arterial/venous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack (TIA), deep vein thrombosis, pulmonary embolism) or other severe thromboembolic events within 6 months prior to first dosing. * Active viral hepatitis with poor control. * Active syphilis requiring treatment. * Active tuberculosis, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or clinically symptomatic active pneumonia. * History of substance abuse that cannot be controlled or presence of psychiatric disorders. * Planned or prior allogeneic bone marrow or solid organ transplantation. * History of hepatic encephalopathy. * History of or current retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), central serous retinopathy (CSR), glaucoma, or other significant ocular abnormalities (e.g., intraocular pressure \>21mmHg). * Inability to undergo MRI and/or presence of MRI contraindications. * Major cardiovascular disease. * Active or uncontrolled severe infection. * Renal failure requiring hemodialysis or peritoneal dialysis. * History of immunodeficiency, including HIV-positive or other acquired/congenital immunodeficiency diseases. * History of epilepsy. * Tumor-related symptoms and treatment. * Known hypersensitivity to study drug excipients. * Participation in and use of other PN clinical trial drugs within 4 weeks prior to first dosing. * Pregnant or lactating participants. * Any other condition that, in the investigator's judgment, poses a serious risk to participant safety or interferes with study completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IRC-Assessed Objective Response Rate (ORR) | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-Assessed ORR | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by investigators per REiNS criteria. |
| IRC/Investigator-Assessed DOR | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | 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. |
| IRC/Investigator-Assessed disease control rate (DCR) | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Percentage of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) as determined by IRC/investigators per REiNS criteria. |
| IRC/Investigator-Assessed progression-free survival (PFS ) | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Time from randomization to first disease progression or death from any cause (whichever occurs first), as determined by IRC/investigators per REiNS criteria. |
| IRC/Investigator-Assessed TTP | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Time from randomization to first disease progression (TTP), as assessed by IRC/investigators per REiNS criteria. |
| IRC/Investigator-Assessed time to response (TTR) | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Time from randomization to first objective response, as determined by IRC/investigators per REiNS criteria. |
| Tumor response in subject | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Difference in the best percentage change from baseline in target PN volume between groups, as assessed by IRC/investigators. |
| Number of subjects with incidence and severity of adverse events (AEs) | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Incidence and severity of adverse events from subject enrollment to the end of cycle 24. |
| Patient-reported outcomes | From subject enrollment to the end of cycle 24 (each cycle is 28 days) | Patient self-assessment results from subject enrollment to the end of cycle 24. |
| Peak concentration (Cmax) | 2 hours after administration | Maximum plasma drug concentration |
| Plasma concentration at steady state (Ctrough, SS) | 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) | The pre-dose concentration observed when the drug has reached steady state with repeated dosing, indicating baseline exposure and accumulation. |
| Effects on pain score in subjects | From subject enrollment to the end of the 24th cycle (each cycle is 28 days) | 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. |
| Effects on pain interference index in subjects | From subject enrollment to the end of the 24th cycle (each cycle is 28 days) | 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 |
| Effects on subjects' general quality of life | From subject enrollment to the end of the 24th cycle (each cycle is 28 days) | 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. |
| Effects on subjects; disease-specific quality of life | From subject enrollment to the end of the 24th cycle (each cycle is 28 days) | Questionnaire: PedsQL NF1 Module; It includes an Adult version (\>25 years) and a Young Adult version (18-25 years), with 104 items, respectively. |
Countries
China
Contacts
CONTACTQingfeng Li, Doctor
Outcome results
None listed