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

Launched by HENAN PROVINCIAL PEOPLE'S HOSPITAL · Aug 21, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a combination treatment of two medications, sintilimab and low-dose bevacizumab, for adults with a specific type of brain tumor called oligodendroglioma that has returned or worsened. The goal is to see if this treatment can help manage the disease better than standard care. The trial is open to adults aged 18 and older who have had surgery to remove their tumor at the study center and meet certain health criteria. Participants will be assigned to one of three groups based on their condition, and they will receive regular monitoring through blood tests and MRI scans.

Eligible participants should have a confirmed diagnosis of oligodendroglioma, be in good health with a life expectancy of at least 12 weeks, and have recovered from surgery. Those who join the study can expect to receive treatment every three weeks, along with ongoing assessments to track their condition. It's important to note that this trial is still recruiting participants, and it aims to improve understanding of how the new treatment works compared to standard care. If you're considering joining the study, it's a good idea to discuss it with your doctor to see if it's the right option for you.

Gender

ALL

Eligibility 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 oligodendroglioma(WHO III)
• • 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 oligodendroglioma
• • 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