Prediction of Therapeutic Response of Apatinib in Recurrent Gliomas

MR and Histopathology Images Based Prediction of Therapeutic Response of Apatinib in Recurrent Gliomas Using Artificial Intelligence

Apatinib, also known as YN968D1, is a small-molecule tyrosine kinase inhibitor (TKI) that selectively binds to and inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). This study aims to collect clinical, radiological and histopathology imaging including detailed radiological data, survival data, clinical parameters, molecular pathology and images of HE slices in patients with recurrent gliomas whose are treated with Apatinib, for evaluating the efficacy and safety of Apatinib. Moreover, by leveraging artificial intelligence, this study seeks to construct and refine MR and histopathology imaging based algorithms that are able to predict the responses to Apatinib of patients with recurrent gliomas.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioma
• Intervention / Treatment: Drug: Apatinib

Detailed Description

Effective treatment for recurrent gliomas is still challenging. Malignant gliomas are considered to be one of the most angiogenic cancers and are mostly sustained by vascular endothelial growth factor (VEGF) signaling via its endothelial tyrosine kinase receptor VEGF receptor 2 (VEGFR-2). Apatinib, also known as YN968D1, is a small-molecule tyrosine kinase inhibitor (TKI) that selectively binds to and inhibits VEGFR-2. Apatinib has been demonstrated as monotherapy that prolongs OS in patients with gastric cancers after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse effects. This study aims to collect clinical, radiological and histopathology imaging including detailed radiological data, survival data, clinical parameters, molecular pathology and images of HE slices in patients with recurrent gliomas whose are treated with Apatinib, for evaluating the efficacy and safety of Apatinib. Moreover, by leveraging artificial intelligence, this study also seeks to construct and refine MR and histopathology imaging based algorithms that are able to predict the responses to Apatinib of patients with recurrent gliomas. The creation of a registry for patients with recurrent gliomas treated by Apatinib with detailed survival data, radiological data, histopathology image data and with sufficient sample size for artificial intelligence provides opportunities for personalized prediction of responses to Apatinib.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Zhenyu Zhang, Dr.; Phone Number: +86 17839973727; Email: fcczhangzy1@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University
      • Contact: Zhenyu Zhang, Dr.; Phone Number: +86 17839973727; Email: fcczhangzy1@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects are all received anti-angiogenesis drug (Apatinib) in the First Affiliated Hospital of Zhengzhou University.

Description

Inclusion Criteria:

1. Adult patients with histologically-confirmed WHO Grade II-IV gliomas which have recurrent or progressive conditions.
2. With measurable or evaluable disease defined by RANO criteria by MRI scan.
3. Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
4. Life expectancy ≥3 months.
5. No evidence of serious cardiopulmonary function damage, postoperative complication and hemorrhage on the baseline.
6. No history of serious hypertension disease.

7. Patients have adequate organ function as defined by the following criteria:

   • Hemoglobin (HGB) ≥90g/L
   • Absolute neutrophil count (ANC) ≥1.5×109/L
   • White blood cell (WBC) ≥3.0×109/L
   • Platelet count ≥80×109/L
   • Alanine aminotransferase(ALT) and Aspartate aminotransferase (AST) of ≤2.5 upper normal limitation (UNL) or ≤5 UNL in case of liver metastasis
   • Creatinine (Cr) of ≤1.25 UNL or creatinine clearance(Ccr) > 45 ml/min.
8. With written informed consent signed voluntarily by patients themselves.

Exclusion Criteria:

1. Patients with age<18 or >90 years.
2. Pregnant or lactating women.
3. Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
4. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
5. Factors that could have an effect on oral medication.
6. Abnormal Coagulation (international normalized ratio>1.5, prothrombin time>UNL+4s,activated partial thromboplastin time>1.5 UNL), with tendency of bleeding.
7. Currently receive thrombolytic and anticoagulation therapy
8. History of pneumorrhagia(CTCAE grade ≥2 ) or other parts hemorrhage(CTCAE grade ≥3 ) within 4 weeks prior to treatment.
9. History of artery thrombosis and phlebothrombosis, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, within 6 month prior to treatment.
10. Medical history of clinically significant thrombosis (bleeding or clotting disorder), excluding warfarin(1mg po qd) and aspirin(80-100mg po qd) for prevention under INR≤1.5.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Apatinib; Apatinib 0.5g orally daily until the untolerable toxicities, disease progression or death	Drug: Apatinib; Apatinib 0.5g orally daily until the untolerable toxicities, disease progression or death

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Response to Treatment	Response were evaluated with Response Assessment in Neuro-Oncology (RANO) criteria every 1 month after treament.	From enrollment to progression of disease. Estimated about 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)	From enrollment to progression of disease. Estimated about 6 months.
Overall Survival (OS)	The length of time from enrollment until the time of death (OS, overall survival)	From enrollment to death of patients. Estimated about 1 year.
Incidence of treatment-related adverse events	The incidence of treatment-related adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.	Time Frame: 0 to 1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: December 31, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Apatinib; Artificial intelligence; Radiological; Therapeutic responses; Histopathology Imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Recurrence; Glioma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: GliomaAI-5

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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