Anlotinib to Malignant Brainstem Glioma

A Phase II Study of Anlotinib Combined With Radiation in Patients With Malignant Brainstem Glioma

This study is a single-arm, open-label, phase II study of anlotinib combined with radiation in the treatment of patients with malignant brainstem glioma. Twenty five patients will be enrolled in the study who is diagonsis with malignant brainstem glioma. The primary objective includes disease control rate (DCR), the role of antinib combined with radiotherapy in improving quality of life and 6-month progression-free survival rate. The secondary objective include overall survival (OS), toxicity profile. Exploratory objectives include the use of plasma specimens and cerebrospinal fluid (if possible) to detect biomarkers predicting the efficacy of anlotinib.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Malignant Brain Stem Tumor
• Intervention / Treatment: Drug: Anlotinib

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuanyuan Chen, Professor; Phone Number: +8613738103808; Email: chenyy@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer hospital
      • Contact: Yuanyuan Chen, Professor; Phone Number: +86 13738103808; Email: chenyy@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign written informed consent before any trial-related processes are implemented;
2. Age ≥ 18 years old and ≤ 70 years old;
3. Life expectancy exceeds 3 months;
4. The investigator confirmed at least one measurable lesion according to the RECIST 1.1 standard. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if it is confirmed to have progressed;
5. Patients with WHO Ⅲ - Ⅳ brain stem glioma confirmed by histology or radiology;
6. The Karnofsky score has to >40;
7. For subjects who had undergone surgical biopsy or treatment, the surgical incision has to be healed well;
8. No prior radiotherapy, chemotherapy, immunotherapy or biotherapy has been performed;

9. Hematological function is sufficient, defined as absolute neutrophil count

   ≥1.5×109 /L, platelet count ≥100 ×109 /L, hemoglobin ≥90g/L (no history of blood transfusion within 7 days);

10. Hepatic function is adequate, defined as all patients with total bilirubin levels ≤ 1.5 times normal upper limit (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN, or for patients with liver metastases , AST and ALT levels ≤ 5 times ULN;
11. adequate renal function, defined as creatinine clearance ≥ 45 ml / min (Cockcroft-Gault formula);
12. Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is receiving anticoagulant therapy, as long as the INR or PT is within the range of anticoagulant drugs can;
13. Female subjects of childbearing age should be negative for urine or serum pregnancy test within 3 days prior to receiving the first study drug. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required;
14. If there is a risk of conception, male and female patients need to use high-efficiency contraception (ie, an annual failure rate of less than 1%) and continue until at least 180 days after stopping the trial treatment; Note: If abstinence is normal for the subject Lifestyle and preferred methods of contraception can be used as a method of contraception.

Exclusion Criteria:

1. WHO grade I-II glioma or imaging diagnosis of low-level brainstem glioma;
2. Supratentorial gliomas in adults involve the brain stem;
3. Patients with contraindications for MRI;
4. Patients with any signs or history of bleeding physique;
5. Currently participating in interventional clinical research treatment, or receiving other research drugs or research equipment within 4 weeks prior to the first dose;
6. Severe intracranial infection;
7. Any arterial thrombosis, embolism or ischemia occurred within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack. A history of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within 3 months prior to enrollment (implanted IV port or catheter-derived thrombosis, or superficial vein thrombosis is not considered a "serious" thrombosis embolism);
8. Prior or concurrent malignancies excepting for adequately treated skin cancer (non-melanoma), in situ cervical carcinoma or cured malignant disease≥5 years;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anlotinib combined with radiation	Drug: Anlotinib; concurrent using anlotinib combined with radiation plus adjuvant anlotinib after radiotherapy until disease progress or develop into serious adverse events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease control rate	based on RECIST1.1	through study completion, an average of 1 year
6-month progression-free survival rate	proportion of patients with progression-free survival longer than 6 months.	From date of randomization until the date of first documented progression or date of death from any cause, assessed up to 6 months
6-month quality of life deterioration-free survival	quality of life	From date of randomization until the date of first documented progression or date of death from any cause, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	overall survival	From date of randomization until the date of first documented progression or date of death from any cause, assessed up to 6 months

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Infratentorial Neoplasms; Glioma; Brain Stem Neoplasms
• Other Study ID Numbers: IRB-2020-217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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