Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Oligodendroglioma

NCT05512351 | Recruiting Phase 2

• 1 other identifier: HenanPPH-Oli
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Oligodendroglioma

Outcome Measures

Primary Outcomes (2)

• Overall 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.

  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.

  Up to 36 months after beginning therapy]

Secondary Outcomes (6)

• Progression-free survival at 15 months

  Up to 15 months after beginning treatment

• Overall survival

  Up to 5 years after beginning treatment

• Overall response rate

  Up to 5 years after beginning treatment

• Progression-free survival

  Up to 5 years after beginning treatment

• Duration of response

  Up to 5 years after beginning treatment

Study Arms (3)

Cohort 1

EXPERIMENTAL

Subjects with ctDNA-level-relapse Oligodendroglioma before clinical relapse, determined according to the dynamics of TISF ctDNA.

Drug: Tislelizumab plus Bevacizumab

Cohort 2

EXPERIMENTAL

Subjects with clinical-relapse Oligodendroglioma, determined according to the response assessment in neuro-oncology (RANO) criteria for gliomas.

Drug: Tislelizumab plus Bevacizumab

Cohort 3

NO INTERVENTION

Subjects without ctDNA-level-relapse and clinical-relapse Oligodendroglioma.

Interventions

Tislelizumab plus Bevacizumab DRUG

200mg sintilimab plus 3mg/kg bevacizumab every 3 weeks.

Also known as: TYVYT®

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 oligodendroglioma(WHO III)
• 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
• 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

You may not qualify if:

• More than two recurrences of oligodendroglioma
• 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
• Prior history of hypertensive crisis, hypertensive encephalopathy, reversible posterior leukoencephalopathy syndrome (RPLS)
• Prior history of gastrointestinal diverticulitis, perforation, or abscess
• 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
• 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
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month prior to randomization

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead

Study Sites (1)

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

MeSH Terms

Conditions

Oligodendroglioma

Interventions

tislelizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xingyao Bu

  Henan Provincial People's Hospital

  STUDY DIRECTOR

Central Study Contacts

Xingyao Bu, MD, PhD

CONTACT

+86037165580295; xingyaob@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2022
• First Posted: August 23, 2022
• Study Start: December 23, 2022
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 27, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)