Overview

Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for Bevacizumab Refractory Recurrent Glioblastoma

Status:
Recruiting
Trial end date:
2026-12-01
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to evaluate the clinical efficacy and safety of sintilimab (one anti-PD-1 antibody same as nivolumab approved in China) in combination with bevacizumab in patients with recurrent or progressive glioblastoma (GBM) who have progressed on bevacizumab with or without PTEN or TERT gene mutations.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Henan Provincial People's Hospital
Treatments:
Bevacizumab
Criteria
Inclusion Criteria:

1. Written informed consent and HIPAA authorization obtained from the subject/legal
representative prior to performing any protocol-related procedures, including
screening evaluations

2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,
laboratory testing, and other requirements of thestudy, including disease assessment
by MRI and tumor in situ fluid (TISF) collection

3. Histologically confirmed diagnosis of glioma

4. Resection surgery done at the study center (Henan Provincial People'sHospital), with
an reservoir intraoperatively implanted connecting the surgical cavity and the
subscalp for postoperative noninvasive TISF collection

5. An interval of > 28 days and full recovery (i.e., no ongoing safety issues) from
surgical resection prior to grouping

6. Karnofsky performance status (KPS) of 70 or higher

7. Life expectancy > 12 weeks

Exclusion Criteria:

1. More than two recurrences of GBM

2. Presence of extracranial metastatic, significant leptomeningeal disease or tumors
primarily localized to the brainstem or spinal cord

3. Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
may increase the risk associated with study participation or study drug
administration, impair the ability of the subject to receive protocol therapy, or
interfere with the interpretation of study results

4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring chronic and systemic
immunosuppressive treatment, or conditions not expected to recur in the absence of an
external trigger are permitted to enroll. Subjects have any other condition requiring
systemic treatment with corticosteroids or other immunosuppressive agents within 14
days. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone
equivalent are permitted in absence of active autoimmune disease

5. Previous radiation therapy with anything other than standard radiation therapy (i.e.,
focally directed radiation) administered as first line therapy

6. Previous treatment with carmustine wafer except when administered as first line
treatment and at least 6 months prior to randomization

7. Previous bevacizumab or other VEGF or anti-angiogenic treatment

8. Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy

9. Evidence of > Grade 1 CNS hemorrhage on the baseline MRI scan

10. Inadequately controlled hypertension (defined as systolic blood pressure ≥160 mmHg and
/or diastolic blood pressure ≥100 mmHg) within 7 days of first study treatment

11. Prior history of hypertensive crisis, hypertensive encephalopathy, reversible
posterior leukoencephalopathy syndrome (RPLS)

12. Prior history of gastrointestinal diverticulitis, perforation, or abscess

13. Clinically significant (i.e., active) cardiovascular disease, for example
cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction
≤ 6 months prior to study enrollment, unstable angina, New York Heart Association
(NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac
arrhythmia uncontrolled by medication or potentially interfering with protocol
treatment

14. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent arterial thrombosis) within 6 months prior to start of study treatment. Any
previous venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start of
study treatment

15. History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red
blood per episode) within 1 month prior to randomization

16. History or evidence of inherited bleeding diathesis or significant coagulopathy at
risk of bleeding (i.e., in the absence of therapeutic anticoagulation)

17. Current or recent (within 10 days of study enrollment) use of anticoagulants that, in
the opinion of the investigator, would place the subject at significant risk for
bleeding. Prophylactic use of anticoagulants is allowed

18. Surgical procedure (including open biopsy, surgical resection, wound revision, or any
other major surgery involving entry into a body cavity) or significant traumatic
injury within 28 days prior to first study treatment, or anticipation of need for
major surgical procedure during the course of the study

19. Minor surgical procedure (e.g., stereotactic biopsy within 7 days of first study
treatment; placement of a vascular access device within 2 days of first study
treatment)

20. History of intracranial abscess within 6 months prior to randomization

21. History of active gastrointestinal bleeding within 6 months prior to randomization