MAPK pathway related childhood tumors
Conditions
Interventions
Test group:Tolatinib monotherapy
Sponsors
The First Affiliated Hospital,Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
3 Years to 18 Years
Inclusion criteria
Inclusion criteria: 1. Informed consent, all participants will provide written informed consent. 2. Enrollment is open to patients of either gender, aged from 3 to 18 years inclusive. 3. Disease Status: The disease is recurrent/refractory to all potential curative standard treatments, or there is no curative therapy for the current disease/no therapy provides a survival benefit while maintaining an acceptable quality of life. 4. Prior Therapy Requirements: For cancer/NF-1 associated plexiform neurofibromas (PN)/Langerhans cell histiocytosis (LCH), must meet: Failure of or relapse after frontline curative-intent therapy. No other curative treatment options are available. Curative-intent therapies include:Surgery/Radiotherapy/Chemotherapy/Combination therapy. 5. Recovery to = 50%. 7. Life expectancy longer than 8 months. 8. Organ Function (all must be met): Renal: 24-hour creatinine clearance (corrected Schwartz formula) or GFR >= 60 mL/min/1.73 m², OR serum creatinine = lower limit of normal (LLN) (assessed by echocardiogram). Blood Pressure: = 1000/µL. Hemoglobin >= 8.0 g/dL (transfusion allowed). Platelets >= 75,000/µL (no platelet transfusion within 7 days prior to enrollment). B. Specific Criteria 1) Genetic testing report of RAS/RAF/MEK/NF1 (MAPK pathway) gene status (mutation positive); 2) Disease status: BRAF tandem duplication fusion-positive low-grade glioma (unresectable/recurrent), NF-1 associated unresectable and clinically significant plexiform neurofibromas, and pediatric tumors with RAS/RAF V600 mutations, etc. — pediatric tumors related to the MAPK pathway.
Exclusion criteria
Exclusion criteria: 1. History of other malignancies (except non-melanoma skin cancer). 2. NF-1 related special circumstances: • Patients with NF-1 associated optic pathway glioma are excluded if they are actively receiving treatment for the optic pathway glioma OR do not meet the criteria for PN or malignant solid tumors. • Subjects with a history of NF-1 related cerebrovascular abnormalities (e.g., moyamoya disease). • NF-1 patients actively receiving treatment for optic pathway glioma. • PN unamenable to volumetric analysis; 3. Severe underlying medical conditions that may affect safety/informed consent/study compliance. 4. Prohibited Medications/Therapies: • Use of or need for medication to treat left ventricular systolic dysfunction. • Prior treatment with dabrafenib / other BRAF inhibitors / trametinib / other MEK inhibitors / ERK inhibitors (sorafenib excepted). Exception: Prior treatment with BRAF inhibitors is acceptable. 5. Treatment Time Window: Received investigational therapy within 30 days prior to study drug administration. 6. Allergy History: Known hypersensitivity to the study drug(s) or their excipients. 7. Organ-specific exclusions: Organ System Exclusion Criteria Liver • Active liver disease (except for Gilbert's syndrome, asymptomatic gallstones, or liver metastases) • History of hepatic sinusoidal obstruction syndrome within the past 3 months Hematologic • History of heparin-induced thrombocytopenia Pulmonary • Presence of interstitial changes (e.g., interstitial lung disease, radiation pneumonitis, or immune-mediated pneumonitis) • Active non-infectious pneumonia, active pulmonary tuberculosis, pneumoconiosis, other types of pneumonia of Grade 2 or higher, OR severely impaired lung function confirmed by tests (FEV1, DLCO, or DLCO/VA=2 NCI-CTCAE v4.0 (except for alopecia) Gastrointestinal • Active gastrointestinal disease that significantly impairs drug absorption (Note: This header is present but no specific items are listed under it in the provided text). 8. Cardiovascular Risks: • QTcB >= 480 milliseconds. • Uncontrolled clinically significant arrhythmia (except atrial fibrillation controlled for >30 days). • History of acute coronary syndrome/coronary intervention within **6 months. • NYHA Class >= II heart failure. • Implanted cardiac defibrillator. • Echocardiogram-confirmed >= Grade 2 cardiac valvular abnormality (mild regurgitation/stenosis is allowed). • Refractory hypertension (systolic BP >140 mmHg / diastolic BP >90 mmHg or >95th percentile for age, AND unresponsive to medication). 9. Active or uncontrolled severe infection (= CTCAE Grade 2 infection) or unexplained fever >38.5°C. 10. Subjects with clinically uncontrolled third-space fluid accumulations (e.g., pleural effusion, ascites, or pericardial effusion) requiring interventions such as drainage are excluded. However, those who have become clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Cognitive function , Quality of life scores, Corticosteroids use;The Disease Control Rate;Progression-free;Safety Analysis;Overall Survival;Duration of Response; | — |
Countries
China
Contacts
Public ContactTang Yanlai
The First Affiliated Hospital,Sun Yat-sen University
Outcome results
None listed