Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma

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 OBJECTIVES:

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.

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)