A Single Arm Clinical Phase Ⅱ Study of Apatinib Combined with Temozolomide and Etoposide Capsules in the Treatment of Recurrent Medulloblastoma in Children

Trial ID: NCT04501718

Interventional - Phase 2 - Recruiting

This study is a prospective single-center clinical study, which aims to observe and evaluate the efficacy and safety of apatinib combined with temozolomide and oral etoposide in the treatment of recurrent medulloblastoma in children.

Conditions

• Recurrent Medulloblastoma

Interventions

• Apatinib Combined With Temozolomide and Etoposide Capsules

Eligibility

Inclusion criteria

• Age 2-21 (at the time of diagnosis), no gender limit.
• 2. After biopsy or surgery, the first postoperative pathological diagnosis is medulloblastoma.
• 3. The recurrence of the tumor is confirmed by MRI, that is, the diameter of the lesion on the enhanced MRI image is ≥1cm, and ≥2 slices (slice spacing 5mm) are visible; or after another biopsy or surgery, the pathological diagnosis is medulloblastoma.
• 4. The time interval from the last radiotherapy is ≥4 weeks.
• 5. The time interval from the last chemotherapy is ≥4 weeks, and the patients have fully recovered from the acute toxicity of the last treatment. If you receive nitrosourea chemotherapeutics before enrollment, the interval between enrollment and the last chemotherapy is ≥6 weeks.
• 6. The interval between the last biopsy or surgery is ≥2 weeks.
• 7. KPS score ≥50 (patient> 12 years old), or Lansky score ≥ 50 (patient ≤ 12 years old).
• 8. If the patient is taking glucocorticoid therapy, the hormone dosage has stabilized or decreased for at least 1 week before the baseline MRI.
• 9. The expected survival time is ≥12 weeks.
• 10. The main organ functions are normal, and there is no serious blood, heart, lung, liver, kidney dysfunction and immune deficiency diseases. The laboratory inspection meets the following requirements:
• (1) Routine blood examination, which must be met (no blood transfusion within 14 days):
• 1. HGB≥100g/L;
• 2. WBC≥3.0×109/L; NEUT≥1.5×109/L;
• 3. PLT ≥100×109/L; (2) The biochemical inspection shall meet the following standards:
• a. BIL≤1.5 times the upper limit of normal (ULN); b. ALT and AST≤2.0×ULN; c. Serum Cr≤1.5×ULN or endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula); (3) Occult blood in stool (-); (4) Urine routine is normal, or urine protein <(++), or 24-hour urine protein <1.0 g; 11. The ECG shows that the heart rate is in the normal range (55-100 beats/min), the QT interval is normal or slightly prolonged (QTc<480ms), the T wave is normal or low, and the ST segment is normal or non-specific changes.
• 12. The coagulation function is normal, without active bleeding and thrombosis.
• 1. International standardized ratio INR≤1.5×ULN;
• 2. Partial thromboplastin time APTT≤1.5×ULN;
• 3. Prothrombin time PT≤1.5ULN. 13. Female patients of childbearing age must undergo a negative pregnancy test (serum or urine) within 7 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration; male patients of childbearing age should agree to During the observation period and within 8 weeks after the last administration, use appropriate methods of contraception.
• 14. Patients voluntarily provide 25-30 slices of tumor tissue after the last biopsy or surgery.
• 15. The patient has normal swallowing function and can swallow capsules. 16. The patient voluntarily joined the study and signed an informed consent form (ICF).
• 17. Those who are expected to have good compliance can follow up the efficacy and adverse reactions as required by the plan.

Exclusion criteria

• Past application of anti-tumor angiogenesis drugs;
• 2. Those who are known to be allergic to any component of temozolomide, apatinib, and etoposide;
• 3. Are using antiepileptic drugs that induce liver drug enzymes, unless they have been replaced with antiepileptic drugs that are non-hepatic drug enzymes at least 2 weeks away from enrollment;
• 4. Patients with other malignant tumors, unless they have survived without progression for 5 years and the researcher believes that the risk of recurrence is low or patients with carcinoma in situ;
• 5. People with hypertension who cannot be reduced to the normal range after treatment with antihypertensive drugs (systolic blood pressure ≤140 mmHg / diastolic blood pressure ≤ 90 mmHg);
• 6. Suffering from severe cardiovascular disease; T wave inverted or high tip of ECG, ST segment specific changes.
• 7. Urine routine test indicates urine protein ≥(++), or 24-hour urine protein ≥1.0g;
• 8. Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 seconds or APTT>1.5×ULN), have bleeding tendency or are receiving thrombolytic or anticoagulant therapy;
• 9. There are many factors that affect the absorption of oral drugs, such as uncontrollable nausea and vomiting, chronic diarrhea and intestinal obstruction;
• 10. There is an infection that is difficult to control;
• 11. Have had significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal perforation, fecal occult blood++ and above at baseline, intratumoral or Intracranial hemorrhage, or suffering from vasculitis, etc.;
• 12. Arterial/venous thrombosis events that occurred within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• 13. Pregnant or breast-feeding women; fertility patients who are unwilling or unable to take effective contraceptive measures;
• 14. Other situations that the researcher thinks are not suitable for inclusion.

Sponsor

Beijing Sanbo Brain Hospital

Source: Clinicaltrials.gov

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