GlioblastomaNCT01939574
A Explore Study of Bevacizumab Combined With Conventional Therapy in Glioblastoma
A study testing Chemoradiation Therapy and Adjuvant Therapy in people with Glioblastoma, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Chemoradiation Therapy and Adjuvant Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Aug 2013to Sep 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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
- Being tested
- Chemoradiation Therapy, Adjuvant Therapy
- Keywords
- Glioblastoma, Potential Image Biomarkers, PFS, Bevacizumab, Conventional Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemoradiation TherapyOther
Also called Radiation therapy, Temozolomide, Bevacizumab
- 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 TherapyOther
Also called Temozolomide, Bevacizumab
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Chemoradiation & Adjuvant Therapy: | Experimental | * 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. Receives: Other: Chemoradiation Therapy; Other: Adjuvant Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At Week 10 of the study
Secondary outcomes (4)
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.
Measured: Up to 106 weeks
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.
Measured: At baseline, on day 22, 70, 127, end of treatment and every 2 months of follow-up
To evaluate health-related quality of life
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30
Measured: On day 1, 22, 71, end of treatment and every 2 months of follow-up
To assess the safety profile
Safety will be measured based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.0
Measured: Up to 106 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study startAug 2013
- Primary completionJun 2016 (estimated)
- Study completionSep 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinming Yu, Shandong Cancer Hospital and Institute
- Investigators
- Jinming Yu, PhD, Study chair, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939574
- Sponsor's protocol ID
- ML28676
- Status last verified
- Jan 2016
- First submitted
- 2 Sep 2013
- Last updated
- 21 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01939574
- Acronym / sponsor ID
- ML28676
- Conditions
- Glioblastoma
- Keywords
- Glioblastoma, Potential Image Biomarkers, PFS, Bevacizumab, Conventional Therapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Sep 2016 (estimated)
- First posted
- 11 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemoradiation & Adjuvant Therapy: | Experimental | Other: Chemoradiation Therapy, Other: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (18 listed)
- Cancer-Related Exclusion Criteria
- Haematologic, Biochemical, Organ Function and other general exclusion criteria
- Contradiction to Bevacizumab treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemoradiation TherapyAlso: Radiation therapy, Temozolomide, Bevacizumab* 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. | Other | Chemoradiation & Adjuvant Therapy: |
| Adjuvant TherapyAlso: Temozolomide, Bevacizumab* 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. | Other | Chemoradiation & Adjuvant Therapy: |
Primary outcome
Correlation between image biomarker change and PFS
Time frame: At Week 10 of the study
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).
4 secondary outcomes
To assess overall survival(OS)
Time frame: Up to 106 weeks
To evaluate the overall response rate (ORR)
Time frame: At baseline, on day 22, 70, 127, end of treatment and every 2 months of follow-up
To evaluate health-related quality of life
Time frame: On day 1, 22, 71, end of treatment and every 2 months of follow-up
To assess the safety profile
Time frame: Up to 106 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jinming Yu, PhD study chair
Shandong Cancer Hospital and Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chemoradiation Therapy and Adjuvant Therapy in people with Glioblastoma, run by Shandong Cancer Hospital and Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between image biomarker change and PFS (time frame: At Week 10 of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2016.