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Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2016 by The First People's Hospital of Lianyungang
Sponsor:
Collaborators:
Shandong Cancer Hospital and Institute
The Affiliated Hospital of Medical College of Qingdao University
Yankuang Group General Hospital
Lianyungang Hospital Affiliated Bengbu Medical College
Suzhou Kowloon Hospital
Information provided by (Responsible Party):
The First People's Hospital of Lianyungang
ClinicalTrials.gov Identifier:
NCT02848794
First received: July 22, 2016
Last updated: July 27, 2016
Last verified: July 2016
  Purpose
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.

Condition Intervention Phase
High-grade Glioma
Drug: Apatinib and Irinotecan
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by The First People's Hospital of Lianyungang:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
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)
Arms Assigned Interventions
Experimental: Apatinib+Irinotecan
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.

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.

  Eligibility

Ages Eligible for Study:   15 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 .
  2. With measurable or evaluable disease defined by RECIST 1.1 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 cerebral embolism, cerebral hemorrhage and serious hypertension disease.
  7. 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.
  8. 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.
  9. Patients will take contraceptive measures for the duration of the treatments and 8 weeks after the last treatment.
  10. With written informed consent signed voluntarily by patients themselves.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
  3. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  4. Coronary heart disease greater than ClassⅠ;Ⅰ-level arrhythmia (including QT interval prolongation≥440 ms) together with ClassⅠcardiac dysfunction
  5. Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction).
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02848794

Contacts
Contact: Xiaodong Jiang, Doctor +86018961326201 jxdysy1970@163.com
Contact: Tao YANG, Master +86018961327792 18961327792@163.com

Locations
China, Jiangsu
The First's People Hospital of Lianyungang Not yet recruiting
Lianyungang, Jiangsu, China, 222000
Contact: Xiaodong Jiang, Doctor    +86018961326201    jxdysy1970@163.com   
Contact: Tao Yang, Master    +86018961327792    18961327792@163.com   
Sponsors and Collaborators
The First People's Hospital of Lianyungang
Shandong Cancer Hospital and Institute
The Affiliated Hospital of Medical College of Qingdao University
Yankuang Group General Hospital
Lianyungang Hospital Affiliated Bengbu Medical College
Suzhou Kowloon Hospital
  More Information

Responsible Party: The First People's Hospital of Lianyungang
ClinicalTrials.gov Identifier: NCT02848794     History of Changes
Other Study ID Numbers: AI-001 
Study First Received: July 22, 2016
Last Updated: July 27, 2016
Health Authority: China: National Health and Family Planning Commission
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 27, 2016