Back to resultsA Study of High-Dose Chemoradiation Using Biologically-Based Target Volume Definition in Patients With Glioblastoma
Primary Purpose
Glioma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
High Dose Radiation
Temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Glioma
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma multiforme and gliosarcoma
- Age 18 or older
- Karnofsky performance status (a measure to quantify general well being and activities of daily life; scale ranges from 0 to 100 where 100 is perfect health) of greater than or equal to 70
- Life expectancy of at least 12 weeks
- Adequate bone marrow reserve (hemoglobin greater than or equal to 10, absolute neutrophil count greater than or equal to 1500, platelets greater than or equal to 100,000); acceptable liver function (total bilirubin less than or equal to 2.0 mg/dl, ALT (Alanine Aminotransferase)/AST (Aspartate Aminotransferase) less than or equal to 5 times the normal range); acceptable renal function (serum creatinine less than or equal to 2.0 mg/dl). Eligibility level for hemoglobin may be reached by transfusion.
- Maximal contiguous volume of tumor based on high b-value diffusion MRI < 1/3 volume of brain
- Patients must be registered within 6 weeks of most recent resection.
- Patients must have signed a study-specific informed consent.
Exclusion Criteria:
- Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable, except for Temozolomide or Bevacizumab.
- Evidence of cerebrospinal fluid dissemination (positive cerebrospinal fluid cytology for malignancy or MRI findings consistent with CSF dissemination)
- Evidence of severe concurrent disease requiring treatment
- Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible)
- Patients unable to undergo Magnetic Resonance Imaging exams (MRI) (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses (e.g. pins in artificial joints and surgical pins/clips) or unable to receive gadolinium for MRI, as per the standard UM Department of Radiology MRI screening criteria)
- Patients treated with previous cranial or head/neck radiotherapy leading to radiation field overlap
- Females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. Patients with reproductive potential must agree to use an effective contraceptive method during treatment.
Sites / Locations
- University of Michigan Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
High Dose Chemoradiation
Arm Description
Patients will receive high dose radiation based in part on advanced imaging, and concurrent temozolomide. Four weeks after the completion of chemoradiation, patients will receive adjuvant temozolomide.
Outcomes
Primary Outcome Measures
Overall Survival at 12 Months
Percentage of patients alive at 12 months after completion of chemoradiation
Median Overall Survival
Median overall survival in months
Secondary Outcome Measures
Median Progression-free Survival
From start of RT until disease progression or death, or until date of last imaging follow-up, estimated using Kaplan-Meier. Progression is defined by any of the following: >= 25% increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; appearance of any new lesions; clear progression of non-measurable lesions; or definite clinical deterioration not attributable to causes other than tumor, or to decrease in corticosteroid dose. When pathologic confirmation was unavailable, progression was defined as worsening enhancement based on imaging with or without adjunctive advanced imaging including perfusion MRI or magnetic resonance spectroscopy, when clinically indicated.
Median Change in Tumor Volume From Baseline to Mid-radiation Treatment (Week 4)
Tumor volume will be measured by diffusion MRI and perfusion MRI before treatment start and at mid-treatment.
Percentage of Patients That Experienced Deterioration in Quality of Life (QOL)
Percentage of patients that experienced deterioration in QOL per the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
Percentage of Patients With Failure; Central or In-field vs. Marginal or Distant
Failures will be classified as central or in-field, marginal or distant based on previously published criteria. 1) "central," in which 95% or more of the recurrent tumor volume (Vrecur) was within D95, the region treated to high dose (95% of the prescription dose); 2) "in-field," in which 80% or more of Vrecur was within the D95 isodose surface; 3) "marginal," when between 20 and 80% of Vrecur was inside the D95 surface; 4) "outside," in which less than 20% of Vrecur was inside the D95 surface.
Full Information
NCT ID
NCT02805179
First Posted
May 12, 2016
Last Updated
March 21, 2021
Sponsor
University of Michigan Rogel Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT02805179
Brief Title
A Study of High-Dose Chemoradiation Using Biologically-Based Target Volume Definition in Patients With Glioblastoma
Official Title
Phase II Study of High Dose Radiotherapy and Concurrent Temozolomide Using Biologically-Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
September 22, 2016 (Actual)
Primary Completion Date
February 6, 2020 (Actual)
Study Completion Date
November 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study to determine the safety and effectiveness of high-dose radiation therapy (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma.
Detailed Description
After analysis demonstrated the improved prognostic value of identifying both hypercellular tumor (TVHCV) based on high b-value diffusion-weighted magnetic resonance imaging (DW-MRI) and hyperperfused tumor (TVCBV) based on dynamic contrast-enhanced MRI (DCE-MRI), the study was amended and later-enrolled patients boosted to both TVHCV and TVCBV.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High Dose Chemoradiation
Arm Type
Experimental
Arm Description
Patients will receive high dose radiation based in part on advanced imaging, and concurrent temozolomide. Four weeks after the completion of chemoradiation, patients will receive adjuvant temozolomide.
Intervention Type
Radiation
Intervention Name(s)
High Dose Radiation
Intervention Description
Radiation will be delivered once daily for a total of 30 fractions, five days per week.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
Patients will receive concurrent temozolomide (75 mg/m^2 daily for 6 weeks). Adjuvant temozolomide will be given at 150-200 mg/m^2, D1-5 every 28 days for a minimum of six cycles and will be started approximately four weeks following completion of radiotherapy.
Primary Outcome Measure Information:
Title
Overall Survival at 12 Months
Description
Percentage of patients alive at 12 months after completion of chemoradiation
Time Frame
12 months after completion of chemoradiation
Title
Median Overall Survival
Description
Median overall survival in months
Time Frame
Median follow-up time was 26 months
Secondary Outcome Measure Information:
Title
Median Progression-free Survival
Description
From start of RT until disease progression or death, or until date of last imaging follow-up, estimated using Kaplan-Meier. Progression is defined by any of the following: >= 25% increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; appearance of any new lesions; clear progression of non-measurable lesions; or definite clinical deterioration not attributable to causes other than tumor, or to decrease in corticosteroid dose. When pathologic confirmation was unavailable, progression was defined as worsening enhancement based on imaging with or without adjunctive advanced imaging including perfusion MRI or magnetic resonance spectroscopy, when clinically indicated.
Time Frame
Median follow-up time was 26 months
Title
Median Change in Tumor Volume From Baseline to Mid-radiation Treatment (Week 4)
Description
Tumor volume will be measured by diffusion MRI and perfusion MRI before treatment start and at mid-treatment.
Time Frame
Baseline to Week 4
Title
Percentage of Patients That Experienced Deterioration in Quality of Life (QOL)
Description
Percentage of patients that experienced deterioration in QOL per the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
Time Frame
Baseline to 1 and 7 months
Title
Percentage of Patients With Failure; Central or In-field vs. Marginal or Distant
Description
Failures will be classified as central or in-field, marginal or distant based on previously published criteria. 1) "central," in which 95% or more of the recurrent tumor volume (Vrecur) was within D95, the region treated to high dose (95% of the prescription dose); 2) "in-field," in which 80% or more of Vrecur was within the D95 isodose surface; 3) "marginal," when between 20 and 80% of Vrecur was inside the D95 surface; 4) "outside," in which less than 20% of Vrecur was inside the D95 surface.
Time Frame
Median 26 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma multiforme and gliosarcoma
Age 18 or older
Karnofsky performance status (a measure to quantify general well being and activities of daily life; scale ranges from 0 to 100 where 100 is perfect health) of greater than or equal to 70
Life expectancy of at least 12 weeks
Adequate bone marrow reserve (hemoglobin greater than or equal to 10, absolute neutrophil count greater than or equal to 1500, platelets greater than or equal to 100,000); acceptable liver function (total bilirubin less than or equal to 2.0 mg/dl, ALT (Alanine Aminotransferase)/AST (Aspartate Aminotransferase) less than or equal to 5 times the normal range); acceptable renal function (serum creatinine less than or equal to 2.0 mg/dl). Eligibility level for hemoglobin may be reached by transfusion.
Maximal contiguous volume of tumor based on high b-value diffusion MRI < 1/3 volume of brain
Patients must be registered within 6 weeks of most recent resection.
Patients must have signed a study-specific informed consent.
Exclusion Criteria:
Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable, except for Temozolomide or Bevacizumab.
Evidence of cerebrospinal fluid dissemination (positive cerebrospinal fluid cytology for malignancy or MRI findings consistent with CSF dissemination)
Evidence of severe concurrent disease requiring treatment
Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible)
Patients unable to undergo Magnetic Resonance Imaging exams (MRI) (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses (e.g. pins in artificial joints and surgical pins/clips) or unable to receive gadolinium for MRI, as per the standard UM Department of Radiology MRI screening criteria)
Patients treated with previous cranial or head/neck radiotherapy leading to radiation field overlap
Females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. Patients with reproductive potential must agree to use an effective contraceptive method during treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle Kim, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
9989517
Citation
Lee SW, Fraass BA, Marsh LH, Herbort K, Gebarski SS, Martel MK, Radany EH, Lichter AS, Sandler HM. Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999 Jan 1;43(1):79-88. doi: 10.1016/s0360-3016(98)00266-1.
Results Reference
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A Study of High-Dose Chemoradiation Using Biologically-Based Target Volume Definition in Patients With Glioblastoma
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