Addition of Anlotinib Hydrochloride to the Stupp Regimen Versus the Stupp Regimen Alone for Newly Diagnosed Glioblastoma

Study Overview
=================
Brief Summary
-----------------
For patients with glioblastoma,postoperative radiotherapy combined with concurrent and adjuvant temozolomide (Stupp regimen) has long been considered a standard treatment approach.The treatment outcomes, however, are still dismal, with a median overall survival time of 8-12 months. As a novel small molecule multi-target tyrosine kinase inhibitor, anlotinib hydrochloride has been found to be able to inhibit both tumor angiogenesis and cell growth.Previous studies on recurrent glioblastoma have demonstrated its effectiveness in tumor control with manageable toxicities. The current study is designed to evaluate the efficacy and feasibility of the additional anlotinib hydrochloride to the Stupp regimen for newly diagnosed glioblastoma.

Official Title
-----------------
Addition of Anlotinib Hydrochloride to the Stupp Regimen Versus the Stupp Regimen Alone for Newly Diagnosed Glioblastoma: A Randomized Multicenter Prospective Phase II Study

Conditions
-----------------
Glioblastoma

Intervention / Treatment
-----------------
* Drug: Anlotinib Hydrochloride
* Radiation: Radiation therapy
* Drug: Temozolomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed and histological proven glioblastoma Complete gross resection or subtotal resection Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate bone marrow, liver and renal function Written informed consent Exclusion Criteria: Meningeal carcinomatosis or spinal compression Patients who have previously received chemotherapy, targeted therapy, or anti-angiogenesis Active, known, or suspected autoimmune disease Severe allergy to anlotinib or temozolomide Patient having acute hepatitis virus infection, active tuberculosis, or other acute infectious diseases Uncontrolled mental disorders High risk of bleeding Severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms), according to NYHA criteria; grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50% Contraindicated for MRI examination Recipient of live vaccine prior to the first dose of anlotinib Ready for or previously received organ transplantation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation therapy, Temozolomide and anlotinib<br>Patients will receive standard radiation therapy plus temozolomide (Stupp regimen). Anlotinib hydrochloride will be given with a daily dose of 12 mg for 14 days of a 21-day cycle up to 2 cycles, initiated on the first day of radiation therapy and followed by adjuvant treatment with the same dosing schedule until patients have disease progression or intolerable toxicities. | Drug: Anlotinib Hydrochloride<br>* Anlotinib hydrochloride will be given with a daily dose of 12 mg for 14 days of a 21-day cycle up to 2 cycles, initiated on the first day of radiation therapy and followed by adjuvant treatment with the same dosing schedule until patients have disease progression or intolerable toxicities.<br>Radiation: Radiation therapy<br>* Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy.<br>Drug: Temozolomide<br>* Temozolomide will be administered at a daily dose of 75 mg/m2 until the completion of radiation therapy. Four weeks after the completion of radiation therapy, patients will be given with adjuvant chemotherapy with temozolomide at a dose of 150-200 mg/m2 for 5 days of a 28-day cycle for a total of 6 cycles.<br>|
| Active Comparator: Radiation therapy and temozolomide<br>Patients will receive standard radiation therapy plus temozolomide (Stupp regimen). | Radiation: Radiation therapy<br>* Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy.<br>Drug: Temozolomide<br>* Temozolomide will be administered at a daily dose of 75 mg/m2 until the completion of radiation therapy. Four weeks after the completion of radiation therapy, patients will be given with adjuvant chemotherapy with temozolomide at a dose of 150-200 mg/m2 for 5 days of a 28-day cycle for a total of 6 cycles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years | 
| Objective response rate |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glioblastoma, Anlotinib hydrochloride, Stupp regimen, Temozolomide, Radiation therapy, Tyrosine kinase inhibitor