Phase 2 Study to Evaluate the Clinical Efficacy and Safety of Sintilimab Plus Low-dose Bevacizumab in Patients With Glioblastoma of Different Relapse Stages
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab plus Bevacizumab
- Conditions
- Glioblastoma
- Sponsor
- Henan Provincial People's Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Overall survival rate at 12 months (Cohort 2)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief 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 glioblastoma (GBM).
This study has two non-comparative study groups. Both cohorts will receive the same study drug sintilimab 200mg and bevacizumab 3mg/kg every 3 weeks. A stringent two-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. 60 total participants are expected to participate in this study (30 participants in each cohort).
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 either group reaches the target number, the new participants will be all assigned into the other Cohort.
Detailed Description
Primary study objectives: -To evaluate the clinical efficacy as measured by the overall survival (OS) rate at 12 months (Cohort 2) and OS rate at 18 months (Cohort 1). Secondary study objectives: -To evaluate the safety/tolerability of the study treatment; To compare the OS, progression-free survival and overall response rate of the two study groups. Exploratory objectives: -To evaluate the correlative biomarkers based on TISF ctDNA.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
- •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
- •Histologically confirmed diagnosis of glioblastoma
- •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
- •Previous first line treatment with at least radiotherapy before the study treatment
- •An interval of \> 28 days and full recovery (i.e., no ongoing safety issues) from surgical resection prior to grouping
- •Karnofsky performance status (KPS) of 70 or higher
- •Life expectancy \> 12 weeks
Exclusion Criteria
- •More than two recurrences of GBM
- •Presence of extracranial metastatic, significant leptomeningeal disease or tumors primarily localized to the brainstem or spinal cord
- •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
- •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
- •Previous radiation therapy with anything other than standard radiation therapy (i.e., focally directed radiation) administered as first line therapy
- •Previous treatment with carmustine wafer except when administered as first line treatment and at least 6 months prior to randomization
- •Previous bevacizumab or other VEGF or anti-angiogenic treatment
- •Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy
- •Evidence of \> Grade 1 CNS hemorrhage on the baseline MRI scan
- •Inadequately controlled hypertension (defined as systolic blood pressure ≥160 mmHg and /or diastolic blood pressure ≥100 mmHg) within 7 days of first study treatment
Arms & Interventions
Cohort 1
Subjects with ctDNA-level-relapse glioblastoma before clinical relapse, determined according to the dynamics of TISF ctDNA.
Intervention: Tislelizumab plus Bevacizumab
Cohort 2
Subjects with clinical-relapse glioblastoma, determined according to the response assessment in neuro-oncology (RANO) criteria for gliomas.
Intervention: Tislelizumab plus Bevacizumab
Outcomes
Primary Outcomes
Overall survival rate at 12 months (Cohort 2)
Time Frame: Up to 12 months after beginning therapy
OS-12 is the proportion of participants in the analysis population who remain alive for at least twelve months following initiation of study therapy.
Overall survival rate at 18 months (Cohort 1)
Time Frame: Up to 18 months after beginning therapy
OS-18 is the proportion of participants in the analysis population who remain alive for at least twelve months following initiation of study therapy.
Secondary Outcomes
- Progression-free survival at 6 months(Up to six months after beginning treatment)
- Overall survival(Up to 3 years after beginning treatment)
- Overall response rate(Up to 3 years after beginning treatment)
- Progression-free survival(Up to 3 years after beginning treatment)
- Duration of response(Up to 3 years after beginning treatment)
- Number of participants with treatment-emergent adverse events(Up to 3 months after beginning therapy)