Malignant Glioma
Conditions
Interventions
PD-1 inhibitor group:PD-1 inhibitor 2mg/kg ivgtt Q3W
EVE+PD-1 inhitor group:Everolimus 10mg PO QD+PD-1 inhibitor 2mg/kg ivgtt Q3W
Sponsors
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
5 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Both sexual, be willing and able to provide written informed consent/assent for the trial. Be >/= 18 years of age on day of signing informed consent, 5 to 18 years of age signing informed consent by parents; 2. Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made; 3. Patients must be at first or second relapse and clinically require reoperation for tumor progression within 4 to 6 weeks. Note: Relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation+ chemotherapy). If the participant had a surgical resection for relapsed disease and no antitumor therapy instituted for up to 12 weeks, this is considered one relapse. For participants who had prior therapy for a low grade glioma, the surgical diagnosis of a high grade glioma will be considered first relapse; 4. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion; 5. Molecular diagnosis of tumor tissue: the mutation of PIK3CA gene, KRAS gene mutation, TSC1 gene mutation, PTEN expression decreased, meet the above 2 and above. High expression of PD-L1 in tumor tissue, and tumor infiltrating lymphocytes consider as drug specifically targeting T-cell co-stimulation or checkpoint pathways; 6. Have a performance status of >/= 60 on the Karnofsky Performance Scale (KPS); 7. Have measurable disease consisting of a miaxmal volume of 3 cm^3; 8. Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day; 9. Demonstrate adequate organ function as defined in additional table 1, all screening labs should be performed within 14 days prior to registration: 1) Hematological: Absolute neutrophil count (ANC) >/=1,500 /mcL; Platelets >/=100,000/mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L; 2) Renal: Serum creatinine /= 60 mL/min for subject with creatinine levels > 1.5 * institutional ULN; 3) Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) 1.5 ULN; AST (SGOT) and ALT (SGPT) </= 2.5 * ULN OR </= 5 * ULN for subjects with liver metastases; 11. Female subject of childbearing potential should have a negative serum pregnancy test.
Exclusion criteria
Exclusion criteria: 1. Has been treated previously with bevacizumab; 2. Has tumor localized primarily to the brainstem or spinal cord; 3. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery; 4. Is currently participating in or has participated in a study of an investigational agent or using an investigational device 4 weeks since last dose of agent administration; 5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of dexamethasone total per day or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial; 6. Has evidence of interstitial lung disease or active, non-infectious pneumonitis; 7. Has an active infection requiring systemic therapy; 8. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment; 9. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); 10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Testing not required. Has known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Testing not required; 11. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tumor size;Mortality in 2 years;progression free survival;overall survival; | — |
Countries
China
Contacts
Public ContactYongming Qiu
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed