Glioblastoma, RecurrentPhase 2NCT04267978
Study of Recombinant Human Endostatin Combined with Temozolomide and Irinotecan in Recurrent Gliomas
A Phase 2 study testing recombinant human endostatin,temozolomide,irinotecan in people with Glioblastoma, Recurrent and Lower Grade Glioma, Recurrent, run by Beijing Sanbo Brain Hospital at 1 site in China.
Trial summary
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan, the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about 21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent lower-grade gliomas was 40%. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Glioblastoma, Recurrent, Lower Grade Glioma, Recurrent
- What is being tested?
- recombinant human endostatin,temozolomide,irinotecan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 1 siteChina
- Study dates
- 13 Feb 2020to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤70;
- Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
- Recurrence is pathologically confirmed by another biopsy or surgery, which should have been completed at least 2 weeks before enrollment, or confirmed by the MRI according to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm apart;
- Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
- The time intervals between the last radiotherapy and enrollment are at least 3 months;
- The interval form the last chemotherapy to the study enrollment was at least one interval of chemotherapy with recover from the related toxic effects (except for hair loss and pigmentation);
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- Karnofsky Performance Status ≥ 60;
- If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days before baseline MRI;
- If the patient is receiving enzyme-inducing antiepileptic drugs (EIAEDs), the drugs should be replaced with non-EIAEDs for at least 1 weeks away from enrollment;
- Estimated survival of at least 12 weeks;
- Participants must have adequate organ function as defined by the following criteria (within 7 days before treatment):
- Hematology (No transfusion within 14 days):
- Hemoglobin(HB)≥90g/L;
- Absolute neutrophil count (ANC)≥1.5×109/L;
- Platelet (PLT)≥80×109/L.
- Chemistry:
- Serum bilirubin ≤ 1.5×upper limit of normal (ULN)
- ALT and AST≤2.5ULN；
- Serum creatinine ≤1.5ULN or creatinine clearance rate(CCr)≥60ml/min；
- ECG: heart rate in the normal range (55-100beats/min), normal or slightly prolonged QT interval (QTc<480ms), normal or low T wave, normal or non-specific ST segment changes.
- Both men and women at the gestational age must agree to take adequate contraceptive measures throughout the study period.
- Participants volunteered to participate in the study and signed an informed consent form (ICF)
Who cannot join
- MRI examination is not available (such as pacemaker, metal denture);
- Receiving any other investigational agent.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
- Patients who have received organ transplants.
- Patients with HIV or Treponema pallidum infection.
- Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific changes.
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- Having factors that affect oral drug absorption, such as vomiting, diarrhea and intestinal obstruction
- There were clinically significant bleeding symptoms or clear bleeding tendency in the first 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ and above, intracranial or intracranial hemorrhage, or vasculitis;
- Arteriovenous thrombosis events occurred within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
- Having bleeding disorder and are being treated with thrombolytic or anticoagulant drugs.
- Other conditions considered inappropriate by the researcher for inclusion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Sanbo Brain Hospital
Beijing
Jun-ping Zhang, 86-010-62856798, doczhjp@hotmail.com
About this study
Official title: Open-label Prospective Study of Recombinant Human Endostatin Combined with Cytotoxic Chemotherapy Regimen in the Treatment of Recurrent Gliomas
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan, the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about 21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be determined.
Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A (VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is the prototypical anti-angiogenic drug and received accelerated approval of the United States Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient and most patients' tumors progress just after a median time of 3-5 months. Recombinant human endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown to significantly improve therapeutic efficacy when combining with conventional chemotherapy agents in non-small-cell lung cancer, breast cancer and melanoma.
Read more
In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months, respectively, which were promising compared with that in other studies. Once patients get radiographic remission in a short time (4 months), they may get a long PFS.The combined regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1 months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study were manageable.
On the basis of prior clinical experience, we carry out this prospective trial to confirm the efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with recurrent gliomas.
- Being tested
- recombinant human endostatin,temozolomide,irinotecan
- Medical subject headings
- Glioblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human endostatin,temozolomide,irinotecanDrug
Temozolomide was given orally 200mg/m2 for 5 days in each cycle. Day 1 TMZ was administered 3-6 hours prior to irinotecan.
Irinotecan was administrated 125mg/m2 on day 1 and day 15. Recombinant human endostatin was administrated 15mg/d, daily for 14 days. One treatment cycle was defined as 28 days (4 weeks), even if treatment is held mid-cycle for toxicity.
Treatment was continued until disease progression, patient withdrawal, or unacceptable toxicity.
The maximum number of treatment cycles was 12. After 12 cycles of treatment, if the investigator judges that the subject may continue to benefit from the regimen, the duration of treatment may be extended with the subject's consent.
| Study group | Role | What they receive |
|---|---|---|
| glioblastoma | Experimental | Not described Receives: Drug: recombinant human endostatin,temozolomide,irinotecan |
| lower-grade glioma | Experimental | Not described Receives: Drug: recombinant human endostatin,temozolomide,irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival rate at 6 months
the percentage of participants who remained progression free at 6 months after treatment initiation.
Measured: up to 4 years
Secondary outcomes (4)
objective response rate
the percentage of patients who achieved confirmed complete response or partial response according to the Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: up to 4 years
Progression-free survival
the time interval from treatment initiation to disease progression or death, whichever occurs first.
Measured: up to 4 years
Overall survival
the time interval from treatment initiation to death from any cause.
Measured: up to 4 years
Safety data
Frequency and severity of adverse effects as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start13 Feb 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, RecurrentStudies 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
- Model description
- glioblastoma, lower-grade glioma
- Masking
- None (open label)
- Enrolment
- 109 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Sanbo Brain Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Junping Zhang, Beijing Sanbo Brain Hospital
- Investigators
- Jun-ping Zhang, Principal investigator, Beijing Sanbo Brain Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04267978
- Sponsor's protocol ID
- SBNK-YJ-2019-006-02
- Status last verified
- Oct 2024
- First submitted
- 11 Feb 2020
- Last updated
- 15 Oct 2024
- 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 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Prospective Study of Recombinant Human Endostatin Combined with Cytotoxic Chemotherapy Regimen in the Treatment of Recurrent Gliomas
- ClinicalTrials.gov ID
- NCT04267978
- Acronym / sponsor ID
- SBNK-YJ-2019-006-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 109 participants (estimated)
- Lead sponsor
- Beijing Sanbo Brain HospitalUniversity, hospital or other
- Study start
- 13 Feb 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 13 Feb 2020 (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.
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan, the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about 21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be determined.
Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A (VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is the prototypical anti-angiogenic drug and received accelerated approval of the United States Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient and most patients' tumors progress just after a median time of 3-5 months. Recombinant human endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown to significantly improve therapeutic efficacy when combining with conventional chemotherapy agents in non-small-cell lung cancer, breast cancer and melanoma.
In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months, respectively, which were promising compared with that in other studies. Once patients get radiographic remission in a short time (4 months), they may get a long PFS.The combined regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1 months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study were manageable.
On the basis of prior clinical experience, we carry out this prospective trial to confirm the efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with recurrent gliomas.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- glioblastoma, lower-grade glioma
| Arm | Type | Receives |
|---|---|---|
| glioblastoma | Experimental | Drug: recombinant human endostatin,temozolomide,irinotecan |
| lower-grade glioma | Experimental | Drug: recombinant human endostatin,temozolomide,irinotecan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Age ≥ 18 and ≤70;
- Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
- Recurrence is pathologically confirmed by another biopsy or surgery, which should have been completed at least 2 weeks before enrollment, or confirmed by the MRI according to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm apart;
- Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
- The time intervals between the last radiotherapy and enrollment are at least 3 months;
Key exclusion criteria (11 listed)
- MRI examination is not available (such as pacemaker, metal denture);
- Receiving any other investigational agent.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
- Patients who have received organ transplants.
- Patients with HIV or Treponema pallidum infection.
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 |
|---|---|---|
| recombinant human endostatin,temozolomide,irinotecanTemozolomide was given orally 200mg/m2 for 5 days in each cycle. Day 1 TMZ was administered 3-6 hours prior to irinotecan. Irinotecan was administrated 125mg/m2 on day 1 and day 15. Recombinant human endostatin was administrated 15mg/d, daily for 14 days. One treatment cycle was defined as 28 days (4 weeks), even if treatment is held mid-cycle for toxicity. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxicity. The maximum number of treatment cycles was 12. After 12 cycles of treatment, if the investigator judges that the subject may continue to benefit from the regimen, the duration of treatment may be extended with the subject's consent. | Drug | glioblastoma, lower-grade glioma |
Primary outcome
progression-free survival rate at 6 months
Time frame: up to 4 years
the percentage of participants who remained progression free at 6 months after treatment initiation.
4 secondary outcomes
objective response rate
Time frame: up to 4 years
Progression-free survival
Time frame: up to 4 years
Overall survival
Time frame: up to 4 years
Safety data
Time frame: up to 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- 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. This study is not recruiting at the moment.
Jun-ping Zhang principal investigator
Beijing Sanbo Brain 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 recombinant human endostatin,temozolomide,irinotecan in people with Glioblastoma, Recurrent and Lower Grade Glioma, Recurrent, run by Beijing Sanbo Brain 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 22 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 15 Oct 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jun-ping Zhang (86-010-62856783, doczhjp@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival rate at 6 months (time frame: up to 4 years). 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 15 Oct 2024.