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

NCT ID: NCT05638451

Last Updated: 2024-06-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2024-12-30

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.

Conditions

Recurrent Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sintilimab and Bevacizumab and Temozolomide

single arm study

Group Type: EXPERIMENTAL

Sintilimab plus Bevacizumab and Temozolomide

Intervention Type: DRUG

200mg Sintilimab plus 10mg/kg Bevacizumab very 3 weeks 200 mg/m2/day Temozolomide on days 1-5 out of a 28 days schedule

Interventions

Sintilimab plus Bevacizumab and Temozolomide

200mg Sintilimab plus 10mg/kg Bevacizumab very 3 weeks 200 mg/m2/day Temozolomide on days 1-5 out of a 28 days schedule

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhujiang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Junde Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Zhujiang Hospital

Locations

southern medical university affiliated Zhujiang Hospital

Guangzhou, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Junde Zhang, MD

Role: CONTACT

13002087575@163.com

13002087575

Yujing Tan, PHD

Role: CONTACT

tanyujing-1981@163.com

13560347303

Facility Contacts

Junde Zhang, Doctor

Role: primary

13002087575@163.com

13002087575

Yujing Tan, Doctor

Role: backup

tanyujing-1981@163.com

+8662782356

Other Identifiers

Junde Zhang

Identifier Type: -

Identifier Source: org_study_id