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

Phase 2 Study to Evaluate the Efficacy and Safety of Sintilimab in Combination With Bevacizumab and Temozolomide in Recurrent Glioblastoma (GBM) Patients

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: Sintilimab plus Bevacizumab and Temozolomide

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junde Zhang, MD; Phone Number: 13002087575; Email: 13002087575@163.com
• Study Contact Backup: Name: Yujing Tan, PHD; Phone Number: 13560347303; Email: tanyujing-1981@163.com

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • southern medical university affiliated Zhujiang Hospital
    • Contact: Yujing Tan, Doctor; Phone Number: +8662782356; Email: tanyujing-1981@163.com
    • Contact: Junde Zhang, Doctor; Phone Number: 13002087575; Email: 13002087575@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab and Bevacizumab and Temozolomide; single arm study	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival rate at 6 months	Progression free survival by iRANO criteria	Up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	the time interval from entry to tumor progression, Progression free survival (PFS) by iRANO criteria	Up to two years
Overall survival	the time interval from entry to death from any cause	Up to two years
Objective response rate	rate of Complete Response +Partial Response	Up to two years
Disease control rate	rate of Complete Response +Partial Response+Stable Disease	Up to two years
Median duration of Karnofsky Performance Status(KPS) ≥ 70	Median duration of KPS ≥ 70 during progression-free survival	Up to two years
Frequency and severity of treatment-related adverse events	Frequency and severity of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to two years
Median duration of stable/improved quality of life assessed by EORTC QLQ-C30	the time interval from entry to change of ≥10 points on the EORTC QLQ-C30 without further improvement or disease progression or death	Up to two years
Absolute counts and ratios of immune cell subtypes	Changes of absolute counts and ratios of immune cell subtypes	Day 1 and Day 29 of each cycle

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Investigators: Principal Investigator: Junde Zhang, MD, Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: November 27, 2022
• First Submitted That Met QC Criteria: November 27, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Temozolomide; Bevacizumab
• Other Study ID Numbers: Junde Zhang

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No