Sintilimab in Combination With Bevacizumab and Temozolomide in Recurrent Glioblastoma (GBM) Patients

Launched by ZHUJIANG HOSPITAL · Nov 27, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for patients with recurrent glioblastoma, a type of brain cancer that comes back after initial treatment. The trial is testing a combination of three medications: Sintilimab, Bevacizumab, and Temozolomide. The goal is to see how well this combination works and whether it is safe for patients.

To participate, individuals need to be between 18 and 70 years old, have a confirmed diagnosis of high-grade glioma, and have had at least one recurrence of their glioblastoma. They should also be in relatively good health, with a specific score that measures their ability to perform daily activities. Participants can expect to receive regular medical check-ups during the trial, including imaging tests to monitor their condition and any side effects from the treatment. It's important to note that there are certain health conditions that may prevent someone from joining, such as recent heart issues or other serious illnesses. If you're considering this trial, it's a good idea to discuss it with your doctor for more personalized advice.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Molecular pathological diagnosis was high-grade glioma (2016 World Health Organization (WHO） Grade Ⅲ or Ⅳ);
• • 2. Age 18 - 70 years old, Karnofsky performance status （KPS） score ≥ 70, and the expected survival period is more than 3 months;
• • 3. Primary supratentorial glioblastoma with first or second recurrence
• • 4. Imaging confirmed recurrence (according to RANO criteria);
• • 5. The time of the first medication after enrollment should be more than 4 weeks away from the surgery or the last radiotherapy;
• • 6. Confirmed progression time is ≥4 weeks from the last drug treatment (including adjuvant temozolomide chemotherapy after the completion of concurrent chemoradiotherapy);
• • 7. If the patient is on hormone therapy, the hormone dose must be stable or reduced for at least 7 days before the baseline MRI examination;
• 8. Major organ function within 7 days prior to treatment, meeting the following criteria:
• (1) Routine blood test standards (without blood transfusion within 14 days):
• • 1. Hemoglobin (HB) ≥90 g/L;
• • 2. Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L;
• 3. Platelet (PLT) ≥ 90×10\^9/L; (2) Biochemical examination shall meet the following standards:
• • 4. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
• • 5. Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5 ULN, if with liver metastasis, ALT and AST ≤ 5ULN;
• • 6. Serum creatinine (Cr) ≤1.5 ULN and creatinine clearance rate (CCr) ≥ 60 ml/min; (3) Echocardiography: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%); (4) International normalized ratio (INR), partial thromboplastin time (APTT), prothrombin time (PT) ≤1.5 ULN; 9. Patients voluntarily joined the study and signed informed consent.
• Exclusion Criteria:
• • 1. Prior treatment with immunotherapy;
• • 2. Patients who have had or are currently suffering from other malignant tumors or solid organ or bone marrow transplantation within 5 years. Excludes cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors;
• • 3. Baseline MRI indicates the risk of cerebral hemorrhage or hernia in the past or recent;
• • 4. Pulmonary embolism or deep vein thrombosis within 2 months
• • 5. Unstable angina pectoris, myocardial infarction within past 12 months. Grade 2 or greater congestive heart failure
• • 6. Peptic ulcer, abdominal fistula, gastrointestinal perforation, or abdominal abscess within past 6 months
• • 7. Patients with any physical signs or history of bleeding, regardless of severity;
• • 8. Uncontrollable high blood pressure
• • 9. Patients with liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis;
• • 10. Renal failure requires hemodialysis or peritoneal dialysis;
• • 11. Known history of active infectious pneumonia and active tuberculosis.
• • 12. Requiring escalating or chronic supraphysiologic doses of corticosteroids (\> 4 mg dexamethasone daily) for control of disease
• • 13. Allergic reaction to bevacizumab or any of its excipients
• • 14. Diagnosis of immunodeficiency, including human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• • 15. Active autoimmune disease requiring systemic treatment (i.e., disease modifiers, corticosteroids, or immunosuppressive drugs) within past 2 years. Replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency, etc.) is not considered a systemic form of therapy.
• • 16. Pregnancy or breastfeeding, or pregnancy or birth during the expected test period, from the pre-screening or screening visit until 120 days after the last dose of test treatment.
• • 17. Unable to undergo brain MRI (i.e., pacemaker or any other MRI contraindications).
• • 18. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.

Trial Officials