No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
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Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 – 70
Sex
Any
Trial phase
Phase 2
Study type
Interventional
Purpose
Treatment
Participants needed
109 (estimated)
Sponsor
Beijing Sanbo Brain Hospital · Other
Who this trial is looking for
This trial is looking for adults with recurrent gliomas, such as glioblastoma or lower-grade gliomas. Participants will receive a combination treatment of recombinant human endostatin with other chemotherapy drugs.
Are You a Good Fit for This Trial?
You may be able to join if
I am between 18 and 70 years old.
I have been diagnosed with recurrent glioblastoma or lower-grade glioma.
My cancer has come back and is confirmed by a biopsy or MRI.
I have received standard chemoradiotherapy and at least one cycle of chemotherapy.
It has been at least 3 months since my last radiotherapy.
It has been at least one chemotherapy cycle since my last treatment.
I am in good health with a Karnofsky Performance Status of 60 or above.
I agree to use contraception during the study.
You may not be able to join if
I cannot have an MRI due to medical devices like a pacemaker.
I am currently taking another investigational drug.
I have a history of allergic reactions to similar drugs.
I have received an organ transplant.
I am infected with HIV or syphilis.
I have severe heart disease.
I have had significant bleeding symptoms in the last 3 months.
I have had blood clots in the last 6 months.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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 …
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.
Trial Locations
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Status
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 18 and ≤70;
2. Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
3. Recurrence is pathologically confi…
Inclusion Criteria:
1. Age ≥ 18 and ≤70;
2. Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
3. 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;
4. Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
5. The time intervals between the last radiotherapy and enrollment are at least 3 months;
6. 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);
7. Karnofsky Performance Status ≥ 60;
8. If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days before baseline MRI;
9. 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;
10. Estimated survival of at least 12 weeks;
11. Participants must have adequate organ function as defined by the following criteria (within 7 days before treatment):
1. Hematology (No transfusion within 14 days):
* Hemoglobin(HB)≥90g/L;
* Absolute neutrophil count (ANC)≥1.5×109/L;
* Platelet (PLT)≥80×109/L.
2. 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;
3. 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.
12. Both men and women at the gestational age must agree to take adequate contraceptive measures throughout the study period.
13. Participants volunteered to participate in the study and signed an informed consent form (ICF)
Exclusion Criteria:
1. MRI examination is not available (such as pacemaker, metal denture);
2. Receiving any other investigational agent.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
4. Patients who have received organ transplants.
5. Patients with HIV or Treponema pallidum infection.
6. Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific changes.
7. Having factors that affect oral drug absorption, such as vomiting, diarrhea and intestinal obstruction
8. 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;
9. 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.;
10. Having bleeding disorder and are being treated with thrombolytic or anticoagulant drugs.
11. Other conditions considered inappropriate by the researcher for inclusion.
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