Biologically-based Target Volumes to Treat Newly Diagnosed Glioblastoma

• ClinicalTrials.gov Identifier: NCT03506139
• Recruitment Status: Recruiting
• First Posted: April 23, 2018
• Last Update Posted: July 24, 2019
• Sponsor: John M. Buatti
• Collaborator: Holden Comprehensive Cancer Center
• Information provided by (Responsible Party): John M. Buatti, University of Iowa

Study Description

Brief Summary:

This clinical trial increases radiation to areas of the brain considered to be at risk for cancer. The at-risk areas are identified by a biological MRI scan. The study will look at side effects of the radiation and overall survival.

Condition or disease	Intervention/treatment	Phase
Glioblastoma; Glioblastoma Multiforme	Radiation: External beam radiation therapy	Phase 2

Detailed Description:

This study evaluates if increasing radiation dose to at-risk areas impacts overall survival without causing a decrease in quality of life or an increase in radiation side effects.

Standard radiation dose for glioblastoma (GBM) is 60 Gray in 30 fractions, with patients receiving 1 fraction per day, Monday through Friday.

This trial will use a total of 75 Gray in 30 fractions, with participants receiving 1 fraction per day, Monday through Friday. Participants will still receive the standard chemotherapy (temozolomide) at the standard dose (75 mg/m2, once daily, 7 days a week).

This study also uses a different imaging technique to identify the tumor target and the tissues at risk. Normal imaging techniques will be used to define the standard target volume and will receive the standard radiation dose (60 Gray). A special MRI sequence will identify at risk areas based on diffusion and perfusion abnormalities. This area will receive the higher radiation dose (75 Gray).

Participants will also be asked to complete quality of life questionnaires and neurocognitive evaluations at specific time points. This is to identify any side effects from the higher radiation dose. Preliminary work done at University of Michigan suggests a lack of side effects from the higher dose of radiation.

Study Design

• Study Type: Interventional
• Estimated Enrollment: 40 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Group treated to 75 Gray of radiation to at-risk target
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of High Dose Radiotherapy and Concurrent Temozolomide Using Biologically-based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma
• Actual Study Start Date: May 15, 2019
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Radiation Therapy; External beam radiation therapy delivered to target volume.	Radiation: External beam radiation therapy; Radiotherapy to 75 Gy Radiation delivered 1 fraction / day, Monday through Friday, for a total of 30 fractions; Other Names: radiotherapy; radiation

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 12 months after completing radiation therapy ]
   Estimate 12-month overall survival of GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.

Secondary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: Every 2 months, for up to 60 months after completing radiation therapy, until progression or death from any cause ]
   Estimate progression-free survival (PFS) in GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
2. Identifying tissue at risk of recurrence [ Time Frame: 12 months after completing radiation therapy ]
   Assess the ability of pre-treatment and mid-treatment advanced MRI to determine areas at high risk of recurrence
3. Distinguish progression from pseudoprogression [ Time Frame: 12 months after completing radiation therapy ]
   Assess the ability of post-treatment advanced MRI to distinguish progression from pseudoprogression
4. Adverse events related to treatment [ Time Frame: Weekly during radiation therapy, every 2 months post-radiation therapy for 7 months, then 13 & 19 months post-radiation ]
   Provide descriptive data regarding health-related quality of life (QOL), symptoms and neurocognitive function

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Ability to understand and willingness to provide informed consent
• Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
• Patients must be 18 years of age or older.≥
• Karnofsky performance status ≥ 70
• Minimal life expectancy of 12 weeks.
• Maximal contiguous volume of tumor based on high b-value diffusion MRI and perfusion MRI < 1/3 volume of brain
• Patients must be treated within 6 weeks of most recent resection

Within 21 days of radiation fraction 1, the following blood test parameters must be met:

• Hemoglobin ≥ 10 g/dL (transfusion is acceptable)
• absolute neutrophils ≥ 1500/mm3
• platelet count ≥ 100,000/mm3
• total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome)
• ALT and AST ≤ 5 x ULN
• serum creatinine ≤ 2.0 mg/dL

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 if interval since last treatment cycle completion is >3 years.
• Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).
• Multifocal disease (>1 lobe of involvement) of discontiguous, contrast enhancing disease as seen on conventional MRI
• Evidence of severe concurrent disease requiring treatment
• Known active malignancy as determined by treating medical and radiation oncologist
• Patients unable to undergo MRI exams
• Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring inpatient hospitalization or delay treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise subject safety.
• Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects.
• Nursing mothers declining to discontinue breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide.
• Patients with reproductive potential declining to use an effective contraceptive method during treatment are excluded from this study.

Contacts and Locations

Contacts

Contact: Heather Brown, RN, BAN; (319) 384-7912; heather-brown@uiowa.edu

Contact: Sandy Vollstedt, RN, BSN; (319) 353-7143; sandy-vollstedt@uiowa.edu

Locations

United States, Iowa

University of Iowa Department of Radiation Oncology; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Heather Brown, RN, BAN, OCN 319-384-7912 heather-brown@uiowa.edu

Contact: Sandy Vollstedt, RN, BSN, OCN 319 353 7143 sandy-vollstedt@uiowa.edu

Principal Investigator: John Buatti, M.D.

Sponsors and Collaborators

John M. Buatti

Holden Comprehensive Cancer Center

Investigators

• Principal Investigator: John M. Buatti, MD; University of Iowa

More Information

Publications:

Hamstra DA, Galbán CJ, Meyer CR, Johnson TD, Sundgren PC, Tsien C, Lawrence TS, Junck L, Ross DJ, Rehemtulla A, Ross BD, Chenevert TL. Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. J Clin Oncol. 2008 Jul 10;26(20):3387-94. doi: 10.1200/JCO.2007.15.2363. Epub 2008 Jun 9.

Galbán CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L, Sundgren PC, Johnson TD, Galbán S, Sebolt-Leopold JS, Rehemtulla A, Ross BD. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011 Jul 15;17(14):4751-60. doi: 10.1158/1078-0432.CCR-10-2098. Epub 2011 Apr 28.

• Responsible Party: John M. Buatti, Professor & Chair, Department of Radiation Oncology, University of Iowa
• ClinicalTrials.gov Identifier: NCT03506139 History of Changes
• Other Study ID Numbers: 201801819
• First Posted: April 23, 2018
• Last Update Posted: July 24, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Deidentified Individual participant data will be shared with a signed usage agreement. Additionally, a contract will be required between University of Iowa and the receiving institution.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Upon request
• Access Criteria: Email study contacts with request

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: No
• Pediatric Postmarket Surveillance of a Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by John M. Buatti, University of Iowa:

Radiotherapy; Magnetic Resonance Imaging

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue