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 Oligodendroglioma(WHO III). This study has three non-comparative study groups. Cohort 1 and Cohort 2 will receive the same study drug sintilimab 200mg and bevacizumab 3mg/kg every 3 weeks. Cohort 3 will take only standard treatment. A stringent three-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. 80 total participants are expected to participate in this study (30 participants in Cohort 1 and Cohort 2). 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 Cohort 1 or Cohort 2 reaches the target number, the new participants will be all assigned into the other Cohort. In the third step, if no CTDNA-level or clinical relapse was observed within 60 months after surgery, patients were assigned to Cohort 3 and further analyzed for prognostic biomarkers compared with Cohort 1 and Cohort 2.
Primary study objectives: -To evaluate the clinical efficacy as measured by the overall survival (OS) rate at 30 months (Cohort 2) and OS rate at 36 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. Standard of care: -Surgical removal of tumors followed by adjuvant temozolomide (150-200 mg/m2, days 1-5 every 28 days for up to 12 cycles). The decision to extend TMZ treatment beyond 6 cycles, for up to 12 cycles, was left to the treating investigator. Patients were asked to attend follow-up visits every 3 months after the end of chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
200mg sintilimab plus 3mg/kg bevacizumab every 3 weeks.
Henan Provincial People's Hospital
Zhengzhou, Henan, China
RECRUITINGOverall survival rate at 30 months (Cohort 2)
OS-30 is the proportion of participants in the analysis population who remain alive for at least thirty months following initiation of study therapy.
Time frame: Up to 30 months after beginning therapy
Overall survival rate at 36months (Cohort 1)
OS-36 is the proportion of participants in the analysis population who remain alive for at least thirty-six months following initiation of study therapy.
Time frame: Up to 36 months after beginning therapy]
Progression-free survival at 15 months
The proportion of participants in the analysis population who remain progression-free for at least fifteen months following initiation of study therapy.
Time frame: Up to 15 months after beginning treatment
Overall survival
overall survival, as defined as time from beginning of treatment to death.
Time frame: Up to 5 years after beginning treatment
Overall response rate
Proportion of participants in the analysis population who have complete response (CR) or partial response (PR) using RANO criteria. Participants without efficacy evalaluation data or survival data censored at day 1. Participants without measurable disease will not be included.
Time frame: Up to 5 years after beginning treatment
Progression-free survival
Median time from allocation to first documented disease progression as per RANO or death due to any cause, whichever occurs first.
Time frame: Up to 5 years after beginning treatment
Duration of response
Time from first RANO response to disease progression in participants who achieve a PR or better.
Time frame: Up to 5 years after beginning treatment
Number of participants with treatment-emergent adverse events
Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of durvalumab. AEs are considered to be treatment emergent if they occur or worsen in severity after the first dose of study treatment.
Time frame: Up to 5 years after beginning treatment
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