OligodendrogliomaPhase 2NCT05512351
Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Oligodendroglioma
A Phase 2 study testing Tislelizumab plus Bevacizumab in people with Oligodendroglioma, run by Henan Provincial People's Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oligodendroglioma
- What is being tested?
- Tislelizumab plus Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 23 Dec 2022to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
- Current or recent (within 10 days of study enrollment) use of anticoagulants that, in the opinion of the investigator, would place the subject at significant risk for bleeding. Prophylactic use of anticoagulants is allowed
- Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment, or anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedure (e.g., stereotactic biopsy within 7 days of first study treatment; placement of a vascular access device within 2 days of first study treatment)
- History of intracranial abscess within 6 months prior to randomization
- History of active gastrointestinal bleeding within 6 months prior to randomization
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Subjects unable (due to existent medical condition, e.g., pacemaker or ICD device) or unwilling to have a head contrast enhanced MRI
- Positive test for hepatitis B virus surface antigen (HBV sAg) or detectable hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- History of severe hypersensitivity reaction to any monoclonal antibody
- Patients that require decadron > 4 mg/ day or equivalent of steroids
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003
Xingyao Bu, xingyaob@zzu.edu.cn
About this study
Official title: Phase 2 Study to Evaluate the Clinical Efficacy and Safety of Sintilimab Plus Low-dose Bevacizumab in Patients With Oligodendroglioma of Different Relapse Stages
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.
Read the detailed description
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.
- Conditions
- Oligodendroglioma
- Being tested
- Tislelizumab plus Bevacizumab
- Medical subject headings
- Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab plus BevacizumabDrug
Also called TYVYT®
200mg sintilimab plus 3mg/kg bevacizumab every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects with ctDNA-level-relapse Oligodendroglioma before clinical relapse, determined according to the dynamics of TISF ctDNA. Receives: 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. Receives: Drug: Tislelizumab plus Bevacizumab |
| Cohort 3 | No intervention | Subjects without ctDNA-level-relapse and clinical-relapse Oligodendroglioma. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 36 months after beginning therapy]
Secondary outcomes (6)
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.
Measured: Up to 15 months after beginning treatment
Overall survival
overall survival, as defined as time from beginning of treatment to death.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years after beginning treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study start23 Dec 2022 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OligodendrogliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xingyao Bu, Study director, Henan Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05512351
- Sponsor's protocol ID
- HenanPPH-Oli
- Status last verified
- Aug 2022
- First submitted
- 21 Aug 2022
- Last updated
- 27 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study to Evaluate the Clinical Efficacy and Safety of Sintilimab Plus Low-dose Bevacizumab in Patients With Oligodendroglioma of Different Relapse Stages
- ClinicalTrials.gov ID
- NCT05512351
- Acronym / sponsor ID
- HenanPPH-Oli
- Conditions
- Oligodendroglioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Henan Provincial People's HospitalUniversity, hospital or other
- Study start
- 23 Dec 2022 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 23 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Tislelizumab plus BevacizumabSubjects with ctDNA-level-relapse Oligodendroglioma before clinical relapse, determined according to the dynamics of TISF ctDNA. |
| Cohort 2 | Experimental | Drug: Tislelizumab plus BevacizumabSubjects with clinical-relapse Oligodendroglioma, determined according to the response assessment in neuro-oncology (RANO) criteria for gliomas. |
| Cohort 3 | No intervention | –Subjects without ctDNA-level-relapse and clinical-relapse Oligodendroglioma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tislelizumab plus BevacizumabAlso: TYVYT®200mg sintilimab plus 3mg/kg bevacizumab every 3 weeks. | Drug | Cohort 1, Cohort 2 |
Primary outcome
Overall survival rate at 30 months (Cohort 2)
Time frame: Up to 30 months after beginning therapy
OS-30 is the proportion of participants in the analysis population who remain alive for at least thirty months following initiation of study therapy.
Overall survival rate at 36months (Cohort 1)
Time frame: Up to 36 months after beginning therapy]
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.
6 secondary outcomes
Progression-free survival at 15 months
Time frame: Up to 15 months after beginning treatment
Overall survival
Time frame: Up to 5 years after beginning treatment
Overall response rate
Time frame: Up to 5 years after beginning treatment
Progression-free survival
Time frame: Up to 5 years after beginning treatment
Duration of response
Time frame: Up to 5 years after beginning treatment
Number of participants with treatment-emergent adverse events
Time frame: Up to 5 years after beginning treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xingyao Bu study director
Henan Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab plus Bevacizumab in people with Oligodendroglioma, run by Henan Provincial People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xingyao Bu, MD, PhD (+86037165580295, xingyaob@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival rate at 30 months (Cohort 2) (time frame: Up to 30 months after beginning therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.