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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Anlotinib Hydrochloride; Radiation: Radiation therapy; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Anticipated): 464
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Heming Lu, MD; Phone Number: 86-771-2186-504; Email: gxheminglu@sina.com

Study Locations

• China
  • Guangxi
    • Guilin, Guangxi, China, 541002
      • Nanxishan Hospital of Guangxi Zhuang Autonomous Region
    • Liuzhou, Guangxi, China, 545005
      • Liuzhou Worker's Hospital
    • Liuzhou, Guangxi, China, 545006
      • Liuzhou people's Hospital
    • Nanning, Guangxi, China, 530021
      • People's Hospital of Guangxi Zhuang Autonomous Region
      • Contact: Heming Lu, MD; Phone Number: +86-771-218-6503; Email: gxheminglu@sina.com
      • Principal Investigator: Heming Lu, MD
    • Nanning, Guangxi, China, 530021
      • Affiliated Hospital of Guangxi Medical University
    • Nanning, Guangxi, China, 530021
      • Affiliated Tumor Hospital of Guangxi Medical University
    • Yulin, Guangxi, China, 537000
      • Yulin First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Objective response rate	3 years

Collaborators and Investigators

• Sponsor: People's Hospital of Guangxi
• Collaborators: Liuzhou Workers Hospital; Cancer Hospital of Guangxi Medical University; First Affiliated Hospital of Guangxi Medical University; LiuZhou People's Hospital; Nanxishan Hospital; Affiliated Hospital of Guilin University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Temozolomide; Glioblastoma; Radiation therapy; Tyrosine kinase inhibitor; Anlotinib hydrochloride; Stupp regimen
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: GXPH-19001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No