Irinotecan And Bevacizumab Combined With Re-radiotherapy in Recurrent Glioblastoma

Study Overview
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Brief Summary
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This is a phase I study to observe the safety and efficacy of irinotecan and bevacizumab combined with re-radiotherapy in the treatment of recurrent glioblastoma. The study will provide a higher level of clinical evidence-based evidence for the clinical treatment of recurrent GBM, and fill the guidelines for the treatment of recurrent GBM.

Official Title
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An Open and Single-arm Prospective Clinical Study of the Safety and Efficacy of Irinotecan and Bevacizumab Combined With Re-radiotherapy in the Treatment of Recurrent Glioblastoma

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: Bevacizumab，Irinotecan and Re-radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The initial diagnosis confirmed by histopathology is World Health Organization WHO grade 4 glioma; Surgery, radiotherapy, chemotherapy, and adjuvant chemotherapy (Stupp plan) are performed after the initial diagnosis, and recurrence according to the evaluation of neurotumor response (RANO) criteria and/or confirmed by histopathology; The expected survival period is ≥3 months; Age between 18 and 70 years old; KPS score (KPS) ≥ 70, able to take care of most of life, but occasionally need help from others; There are measurable lesions on the T1 enhancement sequence of the head MRI; Hematopoietic function: hemoglobin ≥90g/L, platelets ≥90×109/L, white blood cells ≥4×109/L (previous chronic anemia 80-90 g/L or previous low white blood cell level 3-4×109/L Or thrombocytopenia 80-90×109/L, but KPS 70-100 can be considered for admission) (The range of normal values can be fine-tuned due to the different standards of tertiary first-class hospitals); Liver function: ALT and AST<1.5 times of high normal (ULN), bilirubin<1.5×ULN; Sign the informed consent form; Agree to participate in follow-up actions. Exclusion Criteria: Other invasive malignant tumors; Re-irradiation after receiving recurrence in the past; Recurrence more than 3 times or evidence that there is a subdural recurrence disease or a tumor with a maximum diameter of more than 6 cm; Treat with vascular endothelial growth factor (VEGF) or VEGFR inhibitor or irinotecan in advance; Pregnant or nursing mothers; Participate in other tests after diagnosis of recurrence; According to CTCAE5.0 standard classification of patients with bleeding above grade 3; Symptomatic peripheral vascular disease; Known allergy to bevacizumab or irinotecan; Patients who are treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs; under the premise that the prothrombin time international normalized ratio (INR) is ≤1.5, the use of small doses of Huafa for preventive purposes is allowed Farin (1 mg orally, once a day) or low-dose aspirin (do not exceed 100 mg per day); Abnormal blood coagulation function, bleeding tendency (such as active peptic ulcer) or receiving thrombolysis or anticoagulation therapy; Arterial/venous thrombotic events that occurred within 6 months before the first medication, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism; Urine routine test showed urine protein ≥++ and confirmed 24-hour urine protein quantification>1.0 g; Long-term unhealed wounds or fractures; Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poor arrhythmia control (including men with QTc interval ≥450 ms, women ≥470 ms); according to NYHA standards, III to Grade IV insufficiency or color Doppler ultrasonography of the heart shows that the left ventricular ejection fraction (LVEF) is less than 50%; Patients with hypertension who cannot be well controlled by a single antihypertensive drug treatment (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg), suffering from myocardial ischemia or myocardial infarction, arrhythmia (including QT room Period ≥440 ms) and degree I cardiac insufficiency; History of organ transplantation; According to the judgment of the researcher, a serious disease that endangers the safety of the patient or affects the completion of the study. Poor overall health, even KPS<60; Unable to understand the purpose of treatment or unwilling to sign the treatment consent form; No capacity for civil conduct or limited capacity for civil conduct.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>irinotecan + bevacizumab + Re-radiotherapy | Drug: Bevacizumab，Irinotecan and Re-radiotherapy<br>* All patients with recurrent glioblastoma will accept irinotecan and bevacizumab combined with re-radiotherapy .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serious adverse events (SAE) | Clinical safety | From baseline to 28 days after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | the time between the date of enrollment of the patient and death from any cause | From the beginning of treatment to death or the last follow-up, approximately 24 months | 
| progression free survival | The time between the patient's enrollment and any documented tumor progression or death from any cause. | From the start of treatment to the date of disease progression or death, up to approximately 24 months |