Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/IIa, Single-Arm, Open Study of Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma|
- Progression-Free Survival (PFS) [ Time Frame: From enrollment to progression of disease. Estimated about 6 months ] [ Designated as safety issue: No ]The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)
- Overall Survival (OS) [ Time Frame: From enrollment to death of patients. Estimated about 1 year ] [ Designated as safety issue: No ]The length of time from enrollment until the time of death (OS, overall survival)
- Objective Response Rate (ORR) [ Time Frame: From enrollment to 2 months after treatment ] [ Designated as safety issue: No ]clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)
- Disease Control Rate (DCR) [ Time Frame: From enrollment to 2 months after treatment ] [ Designated as safety issue: No ]Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) based on RESIST v1.1 criteria.
- Duration of Response（DOR） [ Time Frame: From first documented CR or PR until disease progression or death(up to 1 year) ] [ Designated as safety issue: No ]As measured by RECIST 1.1 criteria and defined as the time from the first documented CR or PR until disease progression or death from any cause.
- Quality of life (QOL) [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]Quality of life (QOL) will be measured using the EORTC QLQ-C30 questionnaires,which consists of 28 questions with answers that range from 1 (Not At All) to 4 (Very Much) and 2 questions that range from 1 (Very Poor) to 7 (Excellent)
- Incidence of treatment-related adverse events [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||July 2016|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Apatinib and irinotecan in treating patients with recurrent high-grade glioma,who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery .
Drug: Apatinib and Irinotecan
Patients were administered at apatinib (850mg po qd) and irinotecan(125mg/m2 d1,8) intravenously every three weeks for up to 6 cycles.Maintenance apatinib (500mg po qd) was administered until disease progression or unacceptable toxicity.
Gliomas account for almost 80% of primary malignant brain tumors, and glioblastoma is the most common subtype. Despite treatment with surgery, radiation, and chemotherapy(Temozolomide) almost all patients with glioma experience recurrence and the median survival for most patients is less than 2 years. In recurrent disease, salvage therapies have been limited and result in minimal improvement in OS. This overwhelming need for improved treatments has driven the development of novel drugs that target glioma biology, specifically anti-VEGF therapies.
Malignant gliomas are considered among the most angiogenic of cancers and are mostly fueled by vascular endothelial growth factor (VEGF) signaling via its endothelial tyrosine kinase receptor VEGF receptor 2 (VEGFR2). Levels of VEGF and its receptor are correlated with the histologic grade of gliomas, with the highest levels present in glioblastoma.Thus glioblastoma has emerged as an attractive tumor in which to conduct clinical trials of novel anti-VEGF agents, such as monoclonal antibodies and tyrosine kinase inhibitors.
Bevacizumab is a recombinant humanized monoclonal antibody that binds all VEGF isoforms, causing reduced tumor vascularization and inhibiting tumor growth. In a single-institute, phase II trial of patients with recurrent high-grade glioma, bevacizumab in combination with irinotecan demonstrated 46% 6-month PFS and 57% OR rates. Following on from the results of this study, another phase II trial was conducted to evaluate the safety and efficacy of bevacizumab alone and in combination with irinotecan, again showing promising results. On the basis this study, as well as a study by Kreisl and colleagues, FDA has approved to bevacizumab for patients with recurrent glioblastoma in 2009. Despite bevacizumab therapy, 6-month progression-free survival (PFS) for relapsed or progressive high-grade gliomas is 30.8% to 50.3%, and median overall survival (OS) is less than 42 week. Thus, recurrent high-grade gliomas remains a largely unmet medical need, which highlights the need for novel and effective therapies.
Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02848794
|Contact: Xiaodong Jiang, Doctorfirstname.lastname@example.org|
|Contact: Tao YANG, Masteremail@example.com|
|The First's People Hospital of Lianyungang||Not yet recruiting|
|Lianyungang, Jiangsu, China, 222000|
|Contact: Xiaodong Jiang, Doctor +86018961326201 firstname.lastname@example.org|
|Contact: Tao Yang, Master +86018961327792 email@example.com|