An Exploratory Study on Camrelizumab Combined with Bevacizumab for Adult Patients with Recurrent Glioblastoma (GBM)
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab and Bevacizumab
- Conditions
- Recurrent Glioblastoma
- Sponsor
- Beijing Sanbo Brain Hospital
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Progression-free survival rate at 6 months
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This study is intend to explore the efficacy and safety of combined treatment of camrelizumab and bevacizumab in adult patients with recurrent glioblastoma.
Detailed Description
There is no effective chemotherapy regimen for recurrent glioblastoma. The antiangiogenic drug bevacizumab has high objective response rate and rapid onset, but the duration of efficacy needs to be improved.The objective response rate of PD-1 monoclonal antibody immunotherapy is low and the onset of the effect is slow, but the effective patients have a long duration of efficacy.The combined treatment of PD-1 monoclonal antibody and bevacizumab may learn from each other to improve the effective rate, shorten the onset time and prolong the duration of efficacy.Studies have shown that bevacizumab can enhance the efficacy of immunotherapy in a variety of cancers, including melanoma, kidney cancer, non-small cell lung cancer, and liver cancer.However, previous studies have shown limited efficacy of PD-1 monoclonal antibody combined with bevacizumab in the treatment of recurrent glioblastoma. In this study, the combination therapy was optimized by introducing induction phase therapy, which is expected to further improve the efficacy. In our previous exploratory treatment of patients with severe recurrent glioblastoma after multiple treatments, the initial efficacy was considerable. The purpose of this study is to evaluate the efficacy and safety of camrelizumab \[a programmed cell death 1 (PD-1) inhibitor\] combined with bevacizumab for adult patients with recurrent glioblastoma.
Investigators
Junping Zhang
Beijing Sanbo Brain Hospital
Beijing Sanbo Brain Hospital
Eligibility Criteria
Inclusion Criteria
- •Age 18\~70, male or female
- •Primary supratentorial glioblastoma with first or second rogression/recurrence
- •IDH1/2 wildtype
- •KPS score ≥70 in patients with the first recurrence and ≥60 in patients with the second recurrence
- •Expected survival ≥12 weeks.
- •The time interval from the last radiotherapy was ≥12 weeks, unless there was new tumor enhancement in the radiological field or clear evidence of tumor hipathology.
- •Radiotherapy and at least one regimen of chemotherapy before recurrence (excluding temozolomide chemotherapy during concurrent radiotherapy).
- •The patients were enrolled after the end of the previous chemotherapy interval and had recovered from the related adverse reactions (except hair loss and pigmentation).
- •The tumor was confirmed to have definite recurrence by MRI, with enhanced lesion diameter ≥1cm and ≥2 layers (layer spacing 5mm), or was confirmed to have recurrence by pathology after re-biopsy or surgery.
- •The time interval between the last operation and the last biopsy was ≥4 weeks or ≥2 weeks at the time of enrollment.
Exclusion Criteria
- •Glioblastoma in the midline (thalamus, brainstem, sellar region, etc.).
- •Patients with initial recurrence had previously received long-term high-dose antiangiogenic drugs (except those with amlotinib or apatinib for less than 1 month and no progress during treatment, except those with intermittent bev dose intensity ≤5mg/ week and ≤3 times) or immunocheckpoint inhibitors, TCR-T, CAR-T, etc.;Patients with secondary recurrence had previously received long-term high-dose therapy of Bev (except for intermittent Bev dose intensity ≤5mg/ week and ≤3 times) or immunocheckpoint inhibitors, TCR-T, or CAR-T.
- •Other study drugs are being used.
- •An allergic reaction or intolerance to any component of the drug used in this study is known.
- •Other malignant tumors in the past 3 years.
- •Subjects who had been systematically treated with corticosteroids (\>4mg/day dexamethasone or other equivalent hormone) or other immunosuppressants within 2 weeks prior to first use of carrelizumab.In the absence of active autoimmune disease, inhaled or topical corticosteroids and hormone replacement therapy with doses less than or equal to 4mg/ day of dexamethasone are permitted.
- •The presence or history of any active autoimmune disease .
- •Uncontrolled hypertension.
- •Myocardial infarction occurred within 6 months prior to enrollment, New York Heart Society Class II heart failure or above, uncontrolled angina pectoris, uncontrolled severe arrhythmias, clinically significant pericardial disease, and electrocardiogram indicating acute ischemia or abnormal active conduction system.
- •Abnormal coagulation function, bleeding tendency or receiving thrombolytic or anticoagulant therapy.
Arms & Interventions
GBM at first relapse
Intervention: Camrelizumab and Bevacizumab
GBM at second relapse
Intervention: Camrelizumab and Bevacizumab
Outcomes
Primary Outcomes
Progression-free survival rate at 6 months
Time Frame: Up to three years
Progression-free survival rate at 6 months
Secondary Outcomes
- ORR(objective response rate)(Up to three years)
- PFS(progression free survival)(Up to three years)
- Median duration of stable/improved quality of life assessed by EORTC QLQ-BN20(Up to three years)
- OS(overall survival)(Up to three years)
- DCR（Disease Control Rate）(Up to three years)
- The correlation between KPS change and efficacy(Up to three years)
- Median duration of KPS ≥ 70(Up to three years)
- Frequency and severity of treatment-related adverse events(Up to three years)
- Median duration of stable/improved quality of life assessed by EORTC QLQ-C30(Up to three years)