Clinical trial NCT05638451: Sintilimab in Combination With Bevacizumab and Temozolomide in Recurrent Glioblastoma (GBM) Patients
Official title: Phase 2 Study to Evaluate the Efficacy and Safety of Sintilimab in Combination With Bevacizumab and Temozolomide in Recurrent Glioblastoma (GBM) Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Recurrent Glioblastoma
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
First posted: 2022-12-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Sintilimab in combination with Bevacizumab and Temozolomide in subjects with recurrent glioblastoma.

Detailed description: This is a phase 2,open-label, multicenter, single-arm study designed to evaluate the efficacy and safety of Sintilimab in combination with Bevacizumab and Temozolomide in subjects with recurrent glioblastoma.

A total of 30 patients will be enrolled in the study and administered Sintilimab in combination with Bevacizumab and Temozolomide. The study treatment will be continued for up to 4 cycles and Sintilimab was maintained until a progression of disease or unacceptable toxicity is confirmed.

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.

Primary outcomes:
measure: Progression free survival rate at 6 months
timeFrame: Up to two years
Secondary outcomes:
measure: Progression free survival
timeFrame: Up to two years
measure: Overall survival
timeFrame: Up to two years
measure: Objective response rate
timeFrame: Up to two years
measure: Disease control rate
timeFrame: Up to two years
measure: Median duration of Karnofsky Performance Status(KPS) ≥ 70
timeFrame: Up to two years
measure: Frequency and severity of treatment-related adverse events
timeFrame: Up to two years
measure: Median duration of stable/improved quality of life assessed by EORTC QLQ-C30
timeFrame: Up to two years
measure: Absolute counts and ratios of immune cell subtypes
timeFrame: Day 1 and Day 29 of each cycle
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: southern medical university affiliated Zhujiang Hospital
Study officials:
affiliation: Zhujiang Hospital
name: Junde Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: