Non-small cell lung cancer
Conditions
Interventions
Recurrent and high-grade gliomas group:Vebreltinib combine with Bevacizumab and Temozolimide. Vebreltinib 200mg bid, Bevacizumab 3-5mg/kg, q2w and Temozolimide150mg/m^2 (5/28). radiotherapy is allowed
Brain diffuse midline glioma group:Vebreltinib 200mg bid, Bevacizumab 3-5mg/kg, q2w and Temozolimide150mg/m^2 (5/28).radiotherapy is allowed, and the dosage and frequency are decided by investigator.
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Sign informed consent; 2. Age >= 18 years; 3. Histologically confirmed high-grade glioma (WHO grade 3-4), recurrent after at least one prior treatment or untreated diffuse midline glioma in the brain; 4. Expected survival time >= 3 months; 5. According to RANO 2.0 criteria, at least one measurable or assessable lesion; 6. KPS >= 60, able to swallow medication and maintain oral administration; 7. Adequate organ and bone marrow function, defined as follows: (1) Complete blood count: absolute neutrophil count >= 1.5×10^9/L; platelet count >= 75×10^9/L; hemoglobin >= 9.0 g/dL; (2) Liver function: total serum bilirubin (TBIL) = 50 mL/min; urine test strip shows protein <2; (4) Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) <= 2.0×ULN; (5) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects may still be eligible if total T3 (or FT3) and FT4 are within the normal range; (6) Cardiac enzyme profile within the normal range (subjects with minor laboratory abnormalities judged by the investigator as clinically insignificant are also allowed to enroll); 8. For female subjects of childbearing potential, a urine or serum pregnancy test must be conducted within 3 days prior to receiving the first dose of the study drug (Cycle 1, Day 1), and the result must be negative. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non-childbearing potential females are defined as those who have been postmenopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy; 9. If there is a risk of pregnancy, all subjects (male or female) must use contraception methods with a failure rate of less than 1% throughout the treatment period and for 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).
Exclusion criteria
Exclusion criteria: 1. Previously received c-Met inhibitors or HGF-targeted drugs; 2. Those unable to undergo cranial MRI examinations; 3. Those found to have active bleeding on cranial CT or MRI scans before enrollment; 4. Major surgery (such as thoracic, abdominal, or pelvic surgery) performed within 4 weeks before starting the study treatment, or the adverse effects of such surgery have not yet resolved; 5. Diagnosis of malignant diseases other than brain glioma within 5 years before starting the study treatment (excluding fully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or fully resected carcinoma in situ; patients who have undergone radical surgery for papillary thyroid carcinoma can also be enrolled); 6. Known history of primary immunodeficiency; 7. Known allergy to the active ingredients or excipients of the study drugs brigatinib, bevacizumab, and temozolomide; 8. Insufficient recovery from toxicities and/or complications caused by any intervention before starting treatment (i.e., = 2; (3) Any arterial thrombosis, embolism or ischemia occurred within 6 months before enrollment in treatment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, etc.; (4) Poor blood pressure control (systolic blood pressure >150 mmHg, diastolic blood pressure >100 mmHg); (5) History of non-infectious pneumonitis requiring glucocorticoid therapy within 1 year before the first dose, or current clinically active interstitial lung disease; (6) Active tuberculosis; (7) Active or uncontrolled infection requiring systemic treatment; (8) Presence of clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction; (9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; (10) Poorly controlled diabetes (fasting blood glucose (FBG) >10mmol/L); (11) Those who showed urine protein = in their urine routine, and confirmed that the 24-hour urine protein quantitative > was 1.0 g; (12) Patients with mental disorders who cannot cooperate with treatment; (13) Those with active bleeding or new thrombotic disease, who are taking therapeutic doses
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progress free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate;during of response;Disease control rate;Overall survival;6,12,18,24 months-Overall survival rate; | — |
Countries
China
Contacts
Public ContactYiqun Cao
Department of Neurosurgery, Fudan University Shanghai Cancer Center,
Outcome results
None listed