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

Sponsor

People's Hospital of Guangxi (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04157478

Collaborator

First Affiliated Hospital of Guangxi Medical University (Other), Cancer Hospital of Guangxi Medical University (Other), Liuzhou Workers Hospital (Other), Nanxishan Hospital (Other), LiuZhou People's Hospital (Other), Affiliated Hospital of Guilin University (Other)

464

Enrollment

Locations

Arms

Anticipated Duration (Months)

66.3

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: Anlotinib Hydrochloride Radiation: Radiation therapy Drug: Temozolomide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

464 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiation therapy, Temozolomide and anlotinib 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 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. Radiation: Radiation therapy Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy. Drug: Temozolomide 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.
Active Comparator: Radiation therapy and temozolomide Patients will receive standard radiation therapy plus temozolomide (Stupp regimen).	Radiation: Radiation therapy Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy. Drug: Temozolomide 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.

Arm

Intervention/Treatment

Experimental: Radiation therapy, Temozolomide and anlotinib

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

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.

Radiation: Radiation therapy

Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy.

Drug: Temozolomide

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.

Active Comparator: Radiation therapy and temozolomide

Patients will receive standard radiation therapy plus temozolomide (Stupp regimen).

Radiation: Radiation therapy

Radiation therapy will be delivered in daily fractions of 2 Gy given 5 days a week for a total of 60 Gy.

Drug: Temozolomide

Outcome Measures

Primary Outcome Measures

Progression-free survival [3 years]

Secondary Outcome Measures

Overall survival [3 years]
Objective response rate [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nanxishan Hospital of Guangxi Zhuang Autonomous Region	Guilin	Guangxi	China	541002
2	Liuzhou Worker's Hospital	Liuzhou	Guangxi	China	545005
3	Liuzhou People's Hospital	Liuzhou	Guangxi	China	545006
4	Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021
5	Affiliated Tumor Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021
6	People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi	China	530021
7	Yulin First Hospital	Yulin	Guangxi	China	537000