Clinical trial NCT05201326: Irinotecan And Bevacizumab Combined With Re-radiotherapy in Recurrent Glioblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Recurrent Glioblastoma
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2022-01-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. The initial diagnosis confirmed by histopathology is World Health Organization WHO grade 4 glioma;
2. 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;
3. The expected survival period is ≥3 months;
4. Age between 18 and 70 years old;
5. KPS score (KPS) ≥ 70, able to take care of most of life, but occasionally need help from others;
6. There are measurable lesions on the T1 enhancement sequence of the head MRI;
7. 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);
8. Liver function: ALT and AST\<1.5 times of high normal (ULN), bilirubin\<1.5×ULN;
9. Sign the informed consent form;
10. Agree to participate in follow-up actions.

Exclusion Criteria:

1. Other invasive malignant tumors;
2. Re-irradiation after receiving recurrence in the past;
3. 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;
4. Treat with vascular endothelial growth factor (VEGF) or VEGFR inhibitor or irinotecan in advance;
5. Pregnant or nursing mothers;
6. Participate in other tests after diagnosis of recurrence;
7. According to CTCAE5.0 standard classification of patients with bleeding above grade 3;
8. Symptomatic peripheral vascular disease;
9. Known allergy to bevacizumab or irinotecan;
10. 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);
11. Abnormal blood coagulation function, bleeding tendency (such as active peptic ulcer) or receiving thrombolysis or anticoagulation therapy;
12. 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;
13. Urine routine test showed urine protein ≥++ and confirmed 24-hour urine protein quantification\>1.0 g;
14. Long-term unhealed wounds or fractures;
15. 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%;
16. 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;
17. History of organ transplantation;
18. According to the judgment of the researcher, a serious disease that endangers the safety of the patient or affects the completion of the study.
19. Poor overall health, even KPS\<60;
20. Unable to understand the purpose of treatment or unwilling to sign the treatment consent form;
21. No capacity for civil conduct or limited capacity for civil conduct.

Primary outcomes:
measure: serious adverse events (SAE)
timeFrame: From baseline to 28 days after the end of treatment
Secondary outcomes:
measure: overall survival
timeFrame: From the beginning of treatment to death or the last follow-up, approximately 24 months
measure: progression free survival
timeFrame: From the start of treatment to the date of disease progression or death, up to approximately 24 months
Other outcomes:
measure: Quality of life score
timeFrame: Receive once every two months until you cannot tolerate toxicity or PD, up to about 24 months
measure: Cognitive function
timeFrame: Receive once every two months until you cannot tolerate toxicity or PD, up to about 24 months
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Jiayi Chen, MD
role: STUDY_DIRECTOR
References: