Overview

Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Astrocytoma

Status:
Enrolling by invitation
Trial end date:
2024-12-01
Target enrollment:
0
Participant gender:
All
Summary
This is an ongoing Phase 2, open-label, single-center, non-randomized study of sintilimab (one anti-PD-1 antibody same as nivolumab approved in China) plus bevacizumab administered in a low dosage schedule in adult (≥ 18 years) participants with a clinical relapse or circulating tumor DNA (ctDNA)-level relapse of Astrocytoma. This study has three non-comparative study groups. Cohort 1 and Cohort 2 will receive the same study drug sintilimab 200mg and bevacizumab 3mg/kg every 3 weeks. Cohort 3 will take only standard treatment. A stringent three-step non-randomized process will be used to assign participants to one of the study groups. Neither participants nor doctors but the researcher can choose which group participants are in. No one knows if one study group is better or worse than the other. 70 total participants are expected to participate in this study (25 participants in Cohort 1 and Cohort 2,20 participants in Cohort 3). Grouping process: After enrollment, under the standard of care, participants will receive regular tumor in situ fluid (fluid within the surgical cavity, TISF) sampling for ctDNA analysis and recceive regular MRI. The researcher will study the TISF ctDNA and imaging dynamics to determine whether the tumor reaches to ctDNA-level (Cohort 1) or clinical relapse (Cohort 2). At the first step, all timely identified as ctDNA-level relapse tumors will be assigned into the Cohort 1 and receive the study drug immediately, those failed to be timely identified will be assigned into the Cohort 2 and receive the study drug after the clinical relapse. At the second step, once Cohort 1 or Cohort 2 reaches the target number, the new participants will be all assigned into the other Cohort. In the third step, if no ctDNA-level or clinical relapse was observed within 60 months after surgery, patients were assigned to Cohort 3 and further analyzed for prognostic biomarkers compared with Cohort 1 and Cohort 2.
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 the study, including disease assessment
by MRI and tumor in situ fluid (TISF) collection

3. Histologically confirmed diagnosis of Astrocytoma

4. Resection surgery done at the study center (Henan Provincial People's Hospital), 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 Astrocytoma

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

22. Serious, non-healing wound, active ulcer, or untreated bone fracture

23. Subjects unable (due to existent medical condition, e.g., pacemaker or ICD device) or
unwilling to have a head contrast enhanced MRI

24. Positive test for hepatitis B virus surface antigen (HBV sAg) or detectable hepatitis
C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection

25. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS)

26. History of severe hypersensitivity reaction to any monoclonal antibody

27. Patients that require decadron > 4 mg/ day or equivalent of steroids