Clinical trial NCT03137888: Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma
Official title: Pilot Study of Spectroscopic MRI-Guided, Dose-Escalated Radiation Therapy for Newly-Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Gliosarcoma
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: University of Miami
name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
First posted: 2017-05-03
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Feasibility as assessed by successful co-registration of sMRI-based treatment volumes with clinical images into the radiation treatment execution platform
timeFrame: Up to 2 years after completion of therapy
measure: Incidence of adverse event assessed by Common Terminology Criteria for Adverse Events version 4.0
timeFrame: Up to 2 years after completion of therapy
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: From the time of surgical resection to the time of either radiographic progression or death, whichever occurs first, assessed at 1 year
Other outcomes:
measure: Early evidence of GBM progression assessed by sMRI
timeFrame: At 2 weeks after start of therapy
measure: Neurocognitive performance: Hopkins Verbal Learning Test
timeFrame: Up to 2 years after completion of therapy
measure: Neurocognitive performance: Controlled Oral Word Association Test
timeFrame: Up to 2 years after completion of therapy
measure: Overall survival (OS)
timeFrame: From the time of surgical resection to the time of death, assessed up to 1 year
measure: Quality of life (QOL): European Organization for Research and Treatment of Cancer
timeFrame: Up to 2 years after completion of therapy
measure: Quality of life (QOL): MD Anderson
timeFrame: Up to 2 years after completion of therapy
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
Study officials:
affiliation: Emory University/Winship Cancer Institute
name: Hui-Kuo Shu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramesh K, Gurbani SS, Mellon EA, Huang V, Goryawala M, Barker PB, Kleinberg L, Shu HG, Shim H, Weinberg BD. The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients. Tomography. 2020 Jun;6(2):93-100. doi: 10.18383/j.tom.2020.00001.
citation: 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.