Clinical trial NCT04216550: Prediction of Therapeutic Response of Apatinib in Recurrent Gliomas
Official title: MR and Histopathology Images Based Prediction of Therapeutic Response of Apatinib in Recurrent Gliomas Using Artificial Intelligence
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Recurrent Glioma
Keywords: Therapeutic responses
Radiological
Histopathology Imaging
Artificial intelligence
Apatinib
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2020-01-02
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects are all received anti-angiogenesis drug (Apatinib) in the First Affiliated Hospital of Zhengzhou University.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes of Response to Treatment
timeFrame: From enrollment to progression of disease. Estimated about 6 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From enrollment to progression of disease. Estimated about 6 months.
measure: Overall Survival (OS)
timeFrame: From enrollment to death of patients. Estimated about 1 year.
measure: Incidence of treatment-related adverse events
timeFrame: Time Frame: 0 to 1 year
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
References: