Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma

• ClinicalTrials.gov Identifier: NCT03137888
• Recruitment Status: Active, not recruiting
• First Posted: May 3, 2017
• Last Update Posted: July 29, 2019
• Sponsor: Emory University
• Collaborators: Johns Hopkins University; University of Miami; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Hui-Kuo Shu, MD, PhD, Emory University

Study Description

Brief Summary:

This pilot clinical trial studies the side effects of spectroscopic magnetic resonance imaging (MRI)-guided radiation therapy and how well it works in treating patients with newly-diagnosed glioblastoma or gliosarcoma. Spectroscopic MRI can show doctors where the extent of tumor is in the brain beyond current clinical MRI scans by mapping areas of high tumor metabolism. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Spectroscopic MRI-guided radiation therapy may work better in treating patients with glioblastoma or gliosarcoma.

Condition or disease	Intervention/treatment	Phase
Glioblastoma; Gliosarcoma	Radiation: Dose-Escalated Radiation Therapy; Procedure: Spectroscopic Magnetic Resonance Imaging; Drug: Temozolomide	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the feasibility of using spectroscopic MRI (sMRI) to guide dose-escalated radiation therapy (RT) for newly-diagnosed glioblastoma (GBM)s.

II. To determine the safety of using sMRI to guide dose-escalated RT for newly-diagnosed GBMs.

SECONDARY OBJECTIVE:

I. To determine whether the progression free survival at 1 year with sMRI-guided, dose-escalated RT is improved for newly-diagnosed GBMs.

TERTIARY OBJECTIVES:

I. To determine whether sMRI-guided, dose-escalated RT increases the overall survival of patients with newly diagnosed GBMs.

II. To determine whether sMRI data obtained after initiation of therapy (at 2 weeks after RT/TMZ start and prior to cycle 1 and 5 of adjuvant temozolomide [TMZ]) will provide early evidence of GBM progression not seen on standard MRIs.

III. To determine whether performance on neurocognitive and quality-of-life (QOL) assessments in newly-diagnosed GBM patients treated with sMRI-guided, dose-escalated RT differ from historical controls.

OUTLINE:

Patients undergo sMRI-guided radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide orally (PO) daily during radiation therapy for up to 42 days.

After completion of study treatment, patients are followed up every 3 months for up to 2 years and then periodically.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Spectroscopic MRI-Guided, Dose-Escalated Radiation Therapy for Newly-Diagnosed Glioblastoma
• Actual Study Start Date: September 20, 2017
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: July 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: sMRI-Guided RT with TMZ; Patients undergo spectroscopic magnetic resonance imaging-guided dose-escalated radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide PO daily during radiation therapy for up to 42 days.

Radiation: Dose-Escalated Radiation Therapy; Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks; Other Names: RT; Radiation Therapy; Procedure: Spectroscopic Magnetic Resonance Imaging; Patients will undergo sMRI scans within a 14 day window prior to starting treatment; Other Names: sMRI; MRSI; Magnetic Resonance Spectroscopic Imaging; Drug: Temozolomide; Given PO; Other Names: Methazolastone; Temcad; Temodal; Temodar; Temomedac; TMZ

Outcome Measures

Primary Outcome Measures :

1. Feasibility as assessed by successful co-registration of sMRI-based treatment volumes with clinical images into the radiation treatment execution platform [ Time Frame: Up to 2 years after completion of therapy ]
   Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment.
2. Incidence of adverse event assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years after completion of therapy ]
   The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT.

Secondary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: From the time of surgical resection to the time of either radiographic progression or death, whichever occurs first, assessed at 1 year ]
   PFS actuarial curves will be assessed and compared to historical controls, and will particularly interested in comparing the 1-year PFS rate which, based on the control arm (receiving standard dose RT with TMZ) of recent GBM trials, is approximately 30% in historical cohorts.

Other Outcome Measures:

1. Early evidence of GBM progression assessed by sMRI [ Time Frame: At 2 weeks after start of therapy ]
   Changes in sMRI parameters over time will be assessed to determine whether they will be able to predict development of recurrence.
2. Neurocognitive performance: Hopkins Verbal Learning Test [ Time Frame: Up to 2 years after completion of therapy ]
   Neurocognitive performance will be assessed by the Hopkins Verbal Learning Test - Revised.
3. Neurocognitive performance: Controlled Oral Word Association Test [ Time Frame: Up to 2 years after completion of therapy ]
   Neurocognitive performance will be assessed by the Controlled Oral Word Association Test (COWAT) from the Multilingual Aphasia Examination.
4. Overall survival (OS) [ Time Frame: From the time of surgical resection to the time of death, assessed up to 1 year ]
   The OS actuarial curve and 1-year OS rate will be assessed and compared to historical controls.
5. Quality of life (QOL): European Organization for Research and Treatment of Cancer [ Time Frame: Up to 2 years after completion of therapy ]
   QOL will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30/Brain Cancer Module-20.
6. Quality of life (QOL): MD Anderson [ Time Frame: Up to 2 years after completion of therapy ]
   QOL will be assessed by the MD Anderson Symptom Inventory Brain Tumor Module.

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:

• Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist
• Patients must be able to have MRI scans

• Patients must have the following lab values ≤ 14 days prior to registration:

  • White blood cell (WBC) ≥ 3,000/µL
  • Absolute neutrophil count (ANC) ≥ 1,500/µL
  • Platelet count of ≥ 75,000/µL
  • Hemoglobin ≥ 9.0 gm/dL (transfusion is allowed to reach minimum level)
  • Serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0 x upper limit of normal (ULN)
  • Bilirubin ≤ 2 x ULN
  • Creatinine ≤ 1.5 mg/dL
• Patients must have a life expectancy of ≥ 12 weeks
• Patients must have a Karnofsky performance status (KPS) ≥ 60
• Patients who are women of childbearing potential must have a negative pregnancy test documented ≤ 14 days prior to registration; this is not specific to dose escalation and is mandatory for standard care for patients being treated with radiation therapy; the cost of this test will be covered by standard of care
• Patients must be able to understand and provide written informed consent
• Members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions
• Patient must be able to swallow capsules
• Patients must be willing to forego other cytotoxic and non-cytotoxic therapies against the tumor while being treated on this protocol

Exclusion Criteria:

• Patients with pacemakers, aneurysm clips, neurostimulators, cochlear implants, metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue are excluded
• Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are excluded
• Patients with a history of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible
• Patients with an active infection or serious intercurrent medical illness are ineligible
• Patients receiving any other investigational agents are excluded
• Patients who have received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor are excluded
• Patients with a history of prior cranial radiation are ineligible
• Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy
• Patients with GBMs located in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: mesial temporal lobe, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum
• The maximum radiation target volume for gross tumor volume 3 (GTV3) is 65 cc (per NRG Oncology guide); patient may be excluded after the first sMRI scan if the GTV3 volume is greater than 65 cc (we anticipate that contrast-enhancing tumor volume [residual tumor volume following tumor resection] would be less than 20 cc)

Contacts and Locations

Locations

United States, Florida

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States, 33136

United States, Georgia

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

United States, Maryland

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Emory University

Johns Hopkins University

University of Miami

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Hui-Kuo Shu, MD, PhD; Emory University/Winship Cancer Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gurbani S, Weinberg B, Cooper L, Mellon E, Schreibmann E, Sheriff S, Maudsley A, Goryawala M, Shu HK, Shim H. The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow. Tomography. 2019 Mar;5(1):184-191. doi: 10.18383/j.tom.2018.00028.

• Responsible Party: Hui-Kuo Shu, MD, PhD, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT03137888 History of Changes
• Other Study ID Numbers: IRB00094188; NCI-2017-00424 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); RAD3383-17 ( Other Identifier: Emory University/Winship Cancer Institute ); R01CA214557 ( U.S. NIH Grant/Contract )
• First Posted: May 3, 2017
• Last Update Posted: July 29, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Glioblastoma; Gliosarcoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents