Combining endostatin with temozolomide and irinotecan for recurrent gliomas

Open-label Prospective Study of Recombinant Human Endostatin Combined with Cytotoxic Chemotherapy Regimen in the Treatment of Recurrent Gliomas

This study is testing if a new combination of endostatin with two existing cancer drugs can help people with recurrent gliomas live longer without their cancer getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 109 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Beijing Sanbo Brain Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Bevacizumab
• Locations: 1 site (Beijing)
• Trial ID: NCT04267978 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of recombinant human endostatin in combination with temozolomide and irinotecan for patients with recurrent gliomas, including glioblastoma and lower-grade gliomas. The study aims to improve progression-free survival rates, which have been suboptimal with current treatments. Participants must have a confirmed diagnosis of recurrent gliomas and meet specific eligibility criteria, including prior treatment history. The trial will assess the safety and effectiveness of this combination therapy in a Phase 2 setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with histopathologically confirmed recurrent glioblastoma or lower-grade gliomas.

Not a fit: Patients with non-recurrent gliomas or those who have not undergone prior standard chemoradiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve progression-free survival for patients with recurrent gliomas.

How similar studies have performed: While anti-angiogenic therapies have shown some success in glioma treatment, this specific combination approach is novel and has not been extensively tested.

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 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.

Where this trial is running

Beijing

• Beijing Sanbo Brain Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Jun-ping Zhang — Beijing Sanbo Brain Hospital
• Study coordinator: Jun-ping Zhang

Conditions Glioblastoma, Recurrent; Lower Grade Glioma, Recurrent