Back to resultsApatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
Primary Purpose
High-grade Glioma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Apatinib and Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for High-grade Glioma
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically-confirmed, high-grade glioma(WHO Ⅲ/Ⅳ) who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery .
- With measurable or evaluable disease defined by RECIST 1.1 criteria by MRI scan.
- Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
- Life expectancy ≥3 months.
- No evidence of serious cardiopulmonary function damage, postoperative complication and hemorrhage on the baseline.
- No history of cerebral embolism, cerebral hemorrhage and serious hypertension disease.
- Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas and mitomycin), radiotherapy and surgery.
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.
- Patients will take contraceptive measures for the duration of the treatments and 8 weeks after the last treatment.
- With written informed consent signed voluntarily by patients themselves.
Exclusion Criteria:
- Pregnant or lactating women.
- Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- Coronary heart disease greater than ClassⅠ;Ⅰ-level arrhythmia (including QT interval prolongation≥440 ms) together with ClassⅠcardiac dysfunction
- Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction).
- Abnormal Coagulation (international normalized ratio>1.5, prothrombin time>UNL+4s,activated partial thromboplastin time>1.5 UNL), with tendency of bleeding.
- Currently receive thrombolytic and anticoagulation therapy
- History of pneumorrhagia(CTCAE grade ≥2 ) or other parts hemorrhage(CTCAE grade ≥3 ) within 4 weeks prior to treatment.
- 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.
- 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.
Sites / Locations
- The First's People Hospital of LianyungangRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Apatinib+Irinotecan
Arm Description
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 .
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)
Secondary Outcome Measures
Overall Survival (OS)
The length of time from enrollment until the time of death (OS, overall survival)
Objective Response Rate (ORR)
clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)
Disease Control Rate (DCR)
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）
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)
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
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.
Full Information
NCT ID
NCT02848794
First Posted
July 22, 2016
Last Updated
June 14, 2017
Sponsor
The First People's Hospital of Lianyungang
Collaborators
Shandong Cancer Hospital and Institute, The Affiliated Hospital of Qingdao University, Yankuang Group General Hospital, Lianyungang Hospital Affiliated Bengbu Medical College, Suzhou Kowloon Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02848794
Brief Title
Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
Official Title
Phase I/IIa, Single-Arm, Open Study of Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2016 (undefined)
Primary Completion Date
July 2018 (Anticipated)
Study Completion Date
July 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First People's Hospital of Lianyungang
Collaborators
Shandong Cancer Hospital and Institute, The Affiliated Hospital of Qingdao University, Yankuang Group General Hospital, Lianyungang Hospital Affiliated Bengbu Medical College, Suzhou Kowloon Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-grade Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Apatinib+Irinotecan
Arm Type
Experimental
Arm Description
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 .
Intervention Type
Drug
Intervention Name(s)
Apatinib and Irinotecan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)
Time Frame
From enrollment to progression of disease. Estimated about 6 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
The length of time from enrollment until the time of death (OS, overall survival)
Time Frame
From enrollment to death of patients. Estimated about 1 year
Title
Objective Response Rate (ORR)
Description
clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)
Time Frame
From enrollment to 2 months after treatment
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
From enrollment to 2 months after treatment
Title
Duration of Response（DOR）
Description
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.
Time Frame
From first documented CR or PR until disease progression or death(up to 1 year)
Title
Quality of life (QOL)
Description
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)
Time Frame
up to 1 year
Title
Incidence of treatment-related adverse events
Description
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
up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with histologically-confirmed, high-grade glioma(WHO Ⅲ/Ⅳ) who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery .
With measurable or evaluable disease defined by RECIST 1.1 criteria by MRI scan.
Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
Life expectancy ≥3 months.
No evidence of serious cardiopulmonary function damage, postoperative complication and hemorrhage on the baseline.
No history of cerebral embolism, cerebral hemorrhage and serious hypertension disease.
Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas and mitomycin), radiotherapy and surgery.
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.
Patients will take contraceptive measures for the duration of the treatments and 8 weeks after the last treatment.
With written informed consent signed voluntarily by patients themselves.
Exclusion Criteria:
Pregnant or lactating women.
Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
New York Heart Association (NYHA) Grade II or greater congestive heart failure.
Coronary heart disease greater than ClassⅠ;Ⅰ-level arrhythmia (including QT interval prolongation≥440 ms) together with ClassⅠcardiac dysfunction
Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction).
Abnormal Coagulation (international normalized ratio>1.5, prothrombin time>UNL+4s,activated partial thromboplastin time>1.5 UNL), with tendency of bleeding.
Currently receive thrombolytic and anticoagulation therapy
History of pneumorrhagia(CTCAE grade ≥2 ) or other parts hemorrhage(CTCAE grade ≥3 ) within 4 weeks prior to treatment.
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodong Jiang, Doctor
Phone
+86018961326201
Email
jxdysy1970@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tao YANG, Master
Phone
+86018961327792
Email
18961327792@163.com
Facility Information:
Facility Name
The First's People Hospital of Lianyungang
City
Lianyungang
State/Province
Jiangsu
ZIP/Postal Code
222000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaodong Jiang, Doctor
Phone
+86018961326201
Email
jxdysy1970@163.com
First Name & Middle Initial & Last Name & Degree
Tao Yang, Master
Phone
+86018961327792
Email
18961327792@163.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29245310
Citation
Wang L, Liang L, Yang T, Qiao Y, Xia Y, Liu L, Li C, Lu P, Jiang X. A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Medicine (Baltimore). 2017 Dec;96(49):e9053. doi: 10.1097/MD.0000000000009053.
Results Reference
derived
Learn more about this trial
Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
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