Personalized Trial in ctDNA-level-relapse Glioblastoma

Trial Title: Personalized Trial in ctDNA-level-relapse Glioblastoma

NCT ID: NCT05539339

Condition: Glioblastoma

Conditions: Official terms:
Glioblastoma

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: Open-label, pilot, umbrella trial

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Other
Intervention name: Individualized intervention based on genomic alterations
Description: Specialized tumor board recommended agents that target the specific recurrence-driving genomic alterations that are determined by serial TISF ctDNA analysis.
Arm group label: Arm 1

Summary: Tumor in situ fluid (TISF) refers to the fluid within the surgical cavity of patients with glioblastoma. Postoperative serial TISF is collected for circulating tumor DNA (ctDNA) analysis and identifying ctDNA-level relapse driven by one or a set of specific genomic alterations before overt imaging recurrence of the tumor. This single-arm open-label prospective pilot feasibility trial recruiting 20 adult patients with ctDNA-level-relapse glioblastoma who are assigned to receive the personalized study treatment based on the genetic profile of their serial TISF ctDNA. It will be aimed to test whether the personalized intervention can prolong the progression-free and overall survival and the feasibility of conducting a full-scale trial.

Criteria for 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 glioblastoma 4. Resection surgery done at the study center (Henan Provincial People's Hospital), with a reservoir intraoperatively implanted connecting the surgical cavity and the subscalp for postoperative noninvasive TISF collection 5. Previous first line treatment with at least radiotherapy 6. An interval of > 28 days and full recovery (i.e., no ongoing safety issues) from surgical resection prior to grouping 7. Karnofsky performance status (KPS) of 70 or higher 8. 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 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Henan Provincial People's Hospital

Address:
City: Zhengzhou
Zip: 450003
Country: China

Start date: December 1, 2022

Completion date: June 1, 2025

Lead sponsor:
Agency: Henan Provincial People's Hospital
Agency class: Other

Source: Henan Provincial People's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05539339