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A Explore Study of Bevacizumab Combined With Conventional Therapy in Glioblastoma

Primary Purpose

Glioblastoma

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Chemoradiation Therapy
Adjuvant Therapy
Sponsored by
Shandong Cancer Hospital and Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Potential Image Biomarkers, PFS, Bevacizumab, Conventional Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically proven newly diagnosis of glioblastoma (WHO grade IV)
  • The tumor must have a supratentorial component
  • The patient must have recovered from the effects of surgery, postoperative infection, and other complications before initial chemoradiation treatment
  • Documentation of steroid doses within 14 days prior to initial chemoradiation treatment
  • Karnofsky performance status ≥ 70;
  • Age ≥ 18
  • Adequate renal function,hepatic function
  • Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to initial chemoradiation treatment
  • Patient must provide study specific informed consent prior to study entry
  • Women of childbearing potential and male participants must practice adequate contraception.
  • For females of child-bearing potential, negative serum pregnancy test within 14 days prior to initial chemoradiation treatment

Exclusion Criteria:

  • Cancer-Related Exclusion Criteria

    • Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥3 years
    • Recurrent or multifocal malignant gliomas
    • Metastases detected below the tentorium or beyond the cranial vault
    • Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
    • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields

  • Haematologic, Biochemical, Organ Function and other general exclusion criteria

    • Unstable angina and/or congestive heart failure within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥ 2mm using the analysis of an EKG performed within 14 days of initial chemoradiation treatment
    • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to initial chemoradiation treatment
    • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
    • Serious and inadequately controlled cardiac arrhythmia
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of initial chemoradiation treatment
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however,that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
    • Inability to undergo MRI (e.g., due to safety reasons,such as presence of a pacemaker) or PET
  • Contradiction to Bevacizumab treatment

Sites / Locations

  • Shandong Cancer Hospital and Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemoradiation & Adjuvant Therapy:

Arm Description

Concurrent chemoradiation Therapy: Radiation therapy:2 Gy will be given daily 5 days per week for a total of 60 Gy over 6 weeks. Temozolomide from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle,at the beginning of the 4th week of radiation. The dose will be 10 mg/kg. Adjuvant Therapy: Temozolomide once per day for 5 consecutive days of a cycle. The starting dose for the first cycle will be 150 mg/m2/day, with a single dose 200 mg/m2/day in subsequent cycles if no treatment-related adverse events> grade 2 are noted. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle. The dose will be 10 mg/kg.

Outcomes

Primary Outcome Measures

Correlation between image biomarker change and PFS
PFS (evaluated by RANO criteria), defined as the interval from start of treatment to investigator-assessed progression or death, whichever occurs first or lost of follow-up. At Week 10 of the study (corresponding to 7 weeks after the commencement of bevacizumab therapy).

Secondary Outcome Measures

To assess overall survival(OS)
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up.
To evaluate the overall response rate (ORR)
ORR is the number of responders (CR, PR) vs. the whole study population.Tumor response will be evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria.
To evaluate health-related quality of life
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30
To assess the safety profile
Safety will be measured based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.0

Full Information

First Posted
September 2, 2013
Last Updated
January 20, 2016
Sponsor
Shandong Cancer Hospital and Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01939574
Brief Title
A Explore Study of Bevacizumab Combined With Conventional Therapy in Glioblastoma
Official Title
An Open-label, Single Arm Study to Explore Whether Potential Image Biomarkers Correlate With Efficacy of Bevacizumab Combined With Conventional Therapy in Newly Diagnosed Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2013 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shandong Cancer Hospital and Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single-center, open-label, single arm study to explore whether potential image biomarkers correlate with efficacy of bevacizumab combined with conventional therapy in newly diagnosed glioblastoma. Despite the increase in therapies available, the median survival of patients with glioblastoma multiforme (GBM) remains less than 15 months. The phase III pivotal study in newly diagnosed GBM also met its co-primary endpoint of progression-free survival (PFS) which further confirm the efficacy of bevacizumab in GBM. Early predicting the efficacy of bevacizumab combined with conventional therapy in newly diagnosed glioblastoma could help us to identify the suitable patients to receive suitable treatment in GBM. Thus, characterizing the blood flow and blood volume in the tumor and their changes during therapy might provide information on vasculature growth or collapse,edema formation, tumor growth, and/or cell death(necrosis) .We decided to investigate whether the estimation of blood circulation in tumor, using MRI,PET could be used as a surrogate marker to predict the early response of GBM to bevacizumab. Several previous studies have demonstrated that the relative cerebral blood volume (rCBV) correlated with the histologic grade of gliomas and investigated the prognostic value of the tumor CBV for survival.In current study, We hypothesized that, the temporal changes during anti-angiogenesis therapy in specific regions of high and low perfusion in glioblastoma might predict the efficacy of bevacizumab.Since there is no mature PET tracer directly image Vascular Endothelial Growth Factor (VEGF) in China,we use 18F-Galacto-arginine-glycine-aspartic acid (RGD)-- a new tracer for PET imaging of αvβ3 by testing Standardized uptake value mean (SUVmean),Standardized uptake value max (SUVmax) and tumor to non-tumor tissue ratios (T/NT) to indirectly reflect the VEGF expression. The integrin αvβ3 is an important receptor affecting tumor growth, local invasiveness, and metastatic potential. Specifically, αvβ3 is highly expressed on activated endothelial cells during angiogenesis. Therefore, in the pilot study, we use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI),dynamic susceptibility-contrast magnetic resonance imaging (DSC-MRI) and 18F-Galacto-RGD PET to explore the potential image biomarkers of bevacizumab used in newly diagnosed glioblastoma.
Detailed Description
20 patients with newly diagnosed histopathologically confirmed glioblastoma (WHO Grade IV) after surgery will be enrolled in the study. All of the patients will receive conventional concurrent chemoradiation and adjuvant temozolomide plus bevacizumab begin > 3 weeks and ≤ 5 weeks after surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Glioblastoma, Potential Image Biomarkers, PFS, Bevacizumab, Conventional Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemoradiation & Adjuvant Therapy:
Arm Type
Experimental
Arm Description
Concurrent chemoradiation Therapy: Radiation therapy:2 Gy will be given daily 5 days per week for a total of 60 Gy over 6 weeks. Temozolomide from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle,at the beginning of the 4th week of radiation. The dose will be 10 mg/kg. Adjuvant Therapy: Temozolomide once per day for 5 consecutive days of a cycle. The starting dose for the first cycle will be 150 mg/m2/day, with a single dose 200 mg/m2/day in subsequent cycles if no treatment-related adverse events> grade 2 are noted. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle. The dose will be 10 mg/kg.
Intervention Type
Other
Intervention Name(s)
Chemoradiation Therapy
Other Intervention Name(s)
Radiation therapy, Temozolomide, Bevacizumab
Intervention Description
Radiation therapy:For both intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) plans, one treatment of 2 Gy will be given daily 5 days per week for a total of 60 Gy over 6 weeks. Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle,at the beginning of the 4th week of radiation. The dose will be 10 mg/kg of actual body weight.
Intervention Type
Other
Intervention Name(s)
Adjuvant Therapy
Other Intervention Name(s)
Temozolomide, Bevacizumab
Intervention Description
Temozolomide will be administered orally once per day for 5 consecutive days (days 1-5) of a 28-day cycle. The starting dose for the first cycle will be 150 mg/m2/day, with a single dose escalation to 200 mg/m2/day in subsequent cycles if no treatment-related adverse events> grade 2 are noted. Bevacizumab will be administered intravenously on days 1 and 15 of each 28-day cycle. The dose will be 10 mg/kg of actual body weight.
Primary Outcome Measure Information:
Title
Correlation between image biomarker change and PFS
Description
PFS (evaluated by RANO criteria), defined as the interval from start of treatment to investigator-assessed progression or death, whichever occurs first or lost of follow-up. At Week 10 of the study (corresponding to 7 weeks after the commencement of bevacizumab therapy).
Time Frame
At Week 10 of the study
Secondary Outcome Measure Information:
Title
To assess overall survival(OS)
Description
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up.
Time Frame
Up to 106 weeks
Title
To evaluate the overall response rate (ORR)
Description
ORR is the number of responders (CR, PR) vs. the whole study population.Tumor response will be evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria.
Time Frame
At baseline, on day 22, 70, 127, end of treatment and every 2 months of follow-up
Title
To evaluate health-related quality of life
Description
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30
Time Frame
On day 1, 22, 71, end of treatment and every 2 months of follow-up
Title
To assess the safety profile
Description
Safety will be measured based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.0
Time Frame
Up to 106 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven newly diagnosis of glioblastoma (WHO grade IV) The tumor must have a supratentorial component The patient must have recovered from the effects of surgery, postoperative infection, and other complications before initial chemoradiation treatment Documentation of steroid doses within 14 days prior to initial chemoradiation treatment Karnofsky performance status ≥ 70; Age ≥ 18 Adequate renal function,hepatic function Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to initial chemoradiation treatment Patient must provide study specific informed consent prior to study entry Women of childbearing potential and male participants must practice adequate contraception. For females of child-bearing potential, negative serum pregnancy test within 14 days prior to initial chemoradiation treatment Exclusion Criteria: Cancer-Related Exclusion Criteria Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥3 years Recurrent or multifocal malignant gliomas Metastases detected below the tentorium or beyond the cranial vault Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields Haematologic, Biochemical, Organ Function and other general exclusion criteria Unstable angina and/or congestive heart failure within the last 6 months Transmural myocardial infarction within the last 6 months Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥ 2mm using the analysis of an EKG performed within 14 days of initial chemoradiation treatment New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to initial chemoradiation treatment History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months Serious and inadequately controlled cardiac arrhythmia Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of initial chemoradiation treatment Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however,that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol Inability to undergo MRI (e.g., due to safety reasons,such as presence of a pacemaker) or PET Contradiction to Bevacizumab treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinming Yu, PhD
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Shandong Cancer Hospital and Institute
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Explore Study of Bevacizumab Combined With Conventional Therapy in Glioblastoma

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