Page 11 - Delaware Medical Journal - May/June 2018

CANCER CLINICAL TRIAL
PROTOCOL OF THE MONTH
NRG CC001: A Randomized Phase III Trial Of Memantine and Whole-Brain Radiotherapy With or Without
Hippocampal Avoidance in Patients With Brain Metastases
Primary Objective:
•Determine whether the addition of HA-WBRT increases time to neurocognitive failure at months 2, 4, 6 and 12 as measured by neurocognitive decline on a battery of tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B.
Secondary Objectives:
•Determine whether the addition of HA-WBRT preserves neurocognitive function at months 2, 4, 6 and 12 as separately measured by each test, the HVLT-R for Total Recall, Delayed Recall, and Delayed Recognition; COWA; and TMT Parts A and B.
•Evaluate the potential benefit of HA-WBRT in symptom burden, as measured by the M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)
•Assessment of quality adjusted survival and health outcomes using the EQ-5D-5L.
•Compare cumulative incidence of progression and overall survival after WBRT versus HA-WBRT. •Compare adverse events between the treatment arms according to the CTCAE v4.0 criteria.
Eligibility Criteria:
Prior to Step 1 Registration:
•Brain metastases outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced MRI performed ≤21 days prior to Step 1 registration. An allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or CT scan demonstrating brain metastases. However, the brain metastases could not have been within 5 mm of either hippocampus.
•Patients must have a post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient
echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2/FLAIR sequence. To yield acceptable image quality, the gadolinium contrast- enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm. This MRI must be obtained ≤21 days prior to step 1 registration.
Prior to Step 2 Registration:
•Baseline neurocognitive assessments must be completed prior to Step 2 registration. Once the upload is complete, within 1 business day a notification will be sent to the RA to proceed to Step 2.
•Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years prior to Step 2 registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis).
•Male or female ≥18 years of age, Karnofsky Performance Status of ≥70 within 28 days prior to Step 2 registration; History and physical examination within 28 days prior to Step 2 registration
•Adequate renal function ≤28 days prior to Step 2 registration.
•Negative serum pregnancy test ≤14 days prior to Step 2. Women of childbearing potential and men who are sexually active must practice adequate contraception while on study.
•Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection. Patients must have completed prior therapy by at least 14 days prior to Step 2 for surgical resection and 7 days for radiosurgery.
Treatment:
Both Arms with dose escalating dose of Memantine for a total of 24 weeks
Arm 1: WBRT 30 Gy/10 fractions + Memantine
Arm 2: WBRT with Hippocampal Avoidance using IMRT 30 Gy/10 fractions + Memantine
For information regarding clinical trials or if you would like to have the list of open protocols emailed to you, please call the Cancer Research Office at (302) 623-4450 or email akee@christianacare.org.
Del Med J | May/June 2018 | Vol. 90 | No. 5 139