Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer
This randomized phase II/III trial studies how well whole-brain radiation therapy works and
compares it with or without hippocampal avoidance in treating patients with small cell lung
cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only
(limited stage) or has spread outside of the lung in which it began or to other parts of the
body (extensive stage). Radiation therapy uses high energy x-rays to kill tumour cells and
shrink tumours. The hippocampus is part of the brain that is important for memory. Avoiding
the hippocampus during whole-brain radiation could decrease the chance of side effects on
memory and thinking. It is not yet known whether giving whole-brain radiation therapy is
more effective with or without hippocampal avoidance in treating patients with small cell
- HVLT-R delayed recall deterioration status, defined using the Reliable Change Index (RCI) (Phase III)
- Intracranial relapse rate (Phase II)
- Cost-effectiveness as measured by the EQ-5D (Phase III)
- Incidence of adverse events (AEs), as measured by the CTCAE v.4 (Phase III)
- Intracranial relapse rate (Phase III)
- Overall survival (Phase III)
- Patient-reported HRQOL, as measured by the EORTC QLQ-C30 and BN20 (Phase III)
- Preservation of neurocognitive function, as measured by neurocognitive decline for HVLT-R, COWA test, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP) score (Phase III)
- Time to neurocognitive failure, where a failure is defined using the RCI criteria, as measured by HVLT-R, COWA test, and TMT Parts A and B (Phase III)
I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance
(HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following
PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component
II. Determine whether HA-PCI reduces the likelihood of 6-month
deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed
recall compared to PCI for patients with SCLC. (Phase III Component [Efficacy])
I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled
Oral Word Association [COWA] test, and Trail Making Test [TMT] parts A and B), after PCI
versus HA-PCI in SCLC.
II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total
Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI
III. Compare patient-reported cognitive functioning and other quality of life domains
(assessed by the European Organization for Research and Treatment of Cancer [EORTC] Quality
of Life Questionnaire [QLQ]-Core [C]30 and BN20) between PCI versus HA-PCI for patients with
IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC.
12-month intracranial relapse rate (at completion of phase III) and time to intracranial
relapse after PCI versus HA-PCI for patients with SCLC.
VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events
VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in
cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.
VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy [IMRT]) and
PCI (3-dimensional conformal radiation therapy [3DCRT]) using the EuroQual (EQ)-5-Dimensions
I. Collect serum, whole blood, and urine for future translational research analyses.
II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and
hippocampal volumetry as potential predictors of cognitive decline and differential benefit
from HAPCI as compared to PCI.
Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks.
ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks.
After completion of study treatment, patients are followed every 3 months for 1 year, then
every 6 months until 3 years and then annually until death.
View this trial on ClinicalTrials.gov