Pilot Study of Anlotinib With STUPP Regimen for Patients With Newly Diagnosed Glioblastoma

Study Overview
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Brief Summary
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The purpose of this study is to test the the efficacy and safety of Anlotinib in combination with STUPP regimen for patients with newly diagnosed glioblastoma.

Official Title
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Pilot Study of Anlotinib in Combination With STUPP Regimen for Treatment of Patients With Newly Diagnosed Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Drug is Anlotinib.
* Drug: Drug is Temozolomide Capsule.
* Radiation: Radiotherapy was initiated 4 to 6 weeks postoperatively.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary, pathologically confirmed glioblastoma, and complete molecular biological marker tests (MGMT, 1p/19q, IDH, TERT, BRAF, p53, EGFR); 2   6 weeks after operation; the surgical incision healed well; Presence of lesions evaluable according to Rano criteria; Aged 18-70 years; Karnofsky performance status (KPS) ≥ 60; The dose of corticosteroid therapy was stable or gradually reduced in the past 5 days; No previous radiotherapy, chemotherapy, immunotherapy, or biologic therapy; Serum hemoglobin ≥ 100 g/L, platelet count ≥ 80 × 109/L, neutrophil count ≥ 1.5 × 109/L; Serum creatinine ≤ 1.25 × ULN or creatinine clearance ≥ 60 mL/min; Serum bilirubin ≤ 1.5 × ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN, alkaline phosphatase ≤ 5 × ULN; Normal coagulation function (PT prolongation does not exceed 3s, APTT prolongation does not exceed 10s); Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and 8 days after administration of the trial drug. Males must agree to use an appropriate method of contraception or be surgically sterile during the trial and after 8 weeks of trial drug administration; Patient is sufficiently compliant with study and follow-up procedures; Patients signed a formal informed consent form to indicate that they understood that the study was in accordance with hospital policy and ethical requirements. Exclusion Criteria: Secondary glioblastoma; Patients with any other malignant tumor before or now, except skin non-melanotic carcinoma or cervical carcinoma in situ; Any other diseases or conditions are contraindications to chemoradiotherapy (such as active phase of infection, within 6 months after cerebral myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy); Pregnant or lactating women; Women and men who are likely to become pregnant but are unwilling to take appropriate contraceptive measures; Evidence of hereditary bleeding constitution or coagulation disorders; Patients requiring anticoagulant therapy due to other diseases;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single-arm<br>single-arm Drug: Anlotinib Drug: Temozolomide Radiotherapy:Radiotherapy was initiated 4 to 6 weeks postoperatively at a dose of 1.8-2.0 Grays (Gy) per fraction for 5 days per week for 6 weeks with a total dose of 54-60 Gy. | Drug: Drug is Anlotinib.<br>* Anlotinib 8 mg/day (Chia-tai Tianqing Pharmaceutical Co., Ltd.) was given orally on days 1 to 14 per 3-week cycle for 2 cycles during concomitant therapy and maximally 8 cycles during adjuvant chemotherapy. One week after discontinuation of adjuvant chemotherapy, anlotinib 8 mg/day was given for maintenance .<br>Drug: Drug is Temozolomide Capsule.<br>* Temozolomide 75 mg/m2/day was taken for maximally 49 days during concurrent chemoradiotherapy. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients received adjuvant temozolomide for 5 days every 28 days, first cycle 150 mg/m2/day and subsequent cycles 200 mg/m2/day for maximally 6 cycles .<br>Radiation: Radiotherapy was initiated 4 to 6 weeks postoperatively.<br>* Radiotherapy was initiated 4 to 6 weeks postoperatively at a dose of 1.8-2.0 Grays (Gy) per fraction for 5 days per week for 6 weeks with a total dose of 54-60 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-Free Survival | from enrollment to progression or death (for any reason),assessed up to 18months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival | from enrollment to death (for any reason).assessed up to 24 months | 
| adverse event | Adverse events are described in terms of CTC AE 5.0 | from enrollment to death (for any reason).assessed up to 24 months | 
| Health-related quality of life | Health-related quality of life are measured by the EORTC-QL30/BN20. | from enrollment to death (for any reason).assessed up to 24 months | 
| Neurocognitive function | Neurocognitive function are measured by John-Hopkins adapted cognitive exam (ACE). | from enrollment to death (for any reason).assessed up to 24 months |