A Explore Study of Bevacizumab Combined With Conventional Therapy in Glioblastoma

NCT ID: NCT01939574

Last Updated: 2016-01-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2016-09-30

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemoradiation & Adjuvant Therapy:

• 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.

Group Type: EXPERIMENTAL

Chemoradiation Therapy

Intervention Type: OTHER

• 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.

Adjuvant Therapy

Intervention Type: OTHER

• 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.

Interventions

Chemoradiation Therapy

• 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

Adjuvant Therapy

• 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.

Intervention Type: OTHER

Other Intervention Names

Radiation therapy; Temozolomide; Bevacizumab; Temozolomide; Bevacizumab

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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong Cancer Hospital and Institute

OTHER

Sponsor Role: lead

Responsible Party

Jinming Yu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jinming Yu, PhD

Role: STUDY_CHAIR

Shandong Cancer Hospital and Institute

Locations

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

Countries

China

Other Identifiers

ML28676

Identifier Type: -

Identifier Source: org_study_id