Clinical trial NCT01797159: Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer
Official title: "A Phase II Trial of Hippocampal-Sparing Cranial Irradiation (PCI) for Small-Cell Lung Cancer (SCLC)"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Small-cell Lung Cancer
SCLC
Small Cell Lung Cancer Limited Stage
Keywords: Prophylactic Cranial Irradiation
PCI
Hippocampal-sparing irradiation
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2013-02-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The Investigators are looking to compare standard treatment for the management of small cell lung cancer (SCLC) which is prophylactic cranial Irradiation (PCI) (shown to be very good in patient survival) with cranial sparing PCI. Although standard of care PCI is successful in patient survival it also has neurologic side-effects. The Investigators are hoping the cranial sparing PCI has the same positive survival results with the added benefit of lowering neurological side-effects.

Detailed description: The standard of care in management of small cell lung cancer consists of chemotherapy plus thoracic radiation followed by prophylactic cranial irradiation (PCI) based on a randomized trial that demonstrated a significant improvement in overall survival (OS) with PCI. Unfortunately radiation therapy to the brain is associated with neurocognitive toxicity, which may be at least in part related to radiation induced injury to neural progenitor cells in the hippocampus. Both human and animal data suggest an inverse relationship between radiation dose to the hippocampus and performance on neuropsychological testing. We hypothesize that hippocampal sparing PCI will allow improved performance on tests of short term memory and executive function compared to a historical control (RTOG 0212) receiving the same dose of conventional PCI. The primary objective of this study is to evaluate performance on the Hopkins Verbal Learning Test-Revised for delayed recall at 6 months following hippocampal-sparing PCI relative to the historical control. Secondary objectives are to estimate: 1) composite cognitive function following hippocampal-sparing PCI relative to the historical control and 2) the rate of metastases in the hippocampus at 2 years following hippocampal-sparing PCI. The long term goal of this research is to reduce the long term sequelae of radiation therapy for both primary and metastatic brain tumors.

Eligibility criteria: Inclusion Criteria:

* Patient must have newly diagnosed and confirmed small-cell lung cancer (SCLC)
* Patient must have a performance status of 1 or higher
* Patients must not have received previous irradiation to the brain
* Patients must have limited stage disease with complete response to chemotherapy and consolidative chest radiotherapy that was documented at least on standard chest x-rays within one month of study entry
* Negative MRI or CT scan of the brain at least one month before protocol entry
* Women of child-bearing potential must have a negative pregnancy test and also agree to use adequate contraceptives while on protocol
* Patient must be able to understand and sign the informed consent document
* Patient must be informed of the investigational aspect to this trial prior to singing the informed consent document

Exclusion Criteria:

* Patients receiving prior external beam irradiation to the head or neck, including any form of stereotactic irradiation
* Radiographic evidence of brain metastases and/or ipsilateral lung metastases/malignant pleural effusion
* Planned concurrent chemotherapy or antitumoral agent during PCI
* Concomitant malignancy or malignancy within the past five years other than nonmelanomatous skin cancer or carcinoma in situ of the cervix
* Patients with minimal pleural effusion evident on chest X-ray; minimal pleural effusion visible on chest CT is allowed.
* Patients with epilepsy requiring permanent oral medication
* Patients must not have a serious medical or psychiatric illness that would, in the opinion of the investigator, prevent informed consent or completion of protocol treatment, and/or follow-up visits.
* Patients may not take Memantine. This is the only eligibility criterion that has been added to those of RTOG 0212, since some physicians might now prescribe Memantine. This medication would not have been given at the time of enrollment on RTOG 0212 and its administration could confound the results of this study.

Primary outcomes:
measure: Effect of Hippocampal-sparing Prophylactic Cranial Irradiation (PCI) on Possible Delayed Recall Toxicity as Assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R) for Delayed Recall
timeFrame: Baseline, 6 months and 12 months post radiation treatment
Secondary outcomes:
measure: Compare Cognitive Function Following Sparing PCI to That of Standard PCI
timeFrame: Baseline
measure: Compare Cognitive Function Following Sparing PCI to That of Standard PCI
timeFrame: 6 months post radiation treatment
measure: Compare Cognitive Function Following Sparing PCI to That of Standard PCI
timeFrame: 12 months post radiation treatment
measure: Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30
timeFrame: Baseline and 6 months post radiation treatment
measure: Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30
timeFrame: Baseline and 12 months post radiation treatment
measure: Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)
timeFrame: Baseline and 6 months post radiation treatment
measure: Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Using the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20).
timeFrame: Baseline and 12 months post radiation treatment
measure: Number Participants With Hippocampus Brain Metastases Following Sparing PCI
timeFrame: 12 months
measure: Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected
timeFrame: 6 months, 12 months, 18 months and 24 months post radiation treatment
measure: Percentage of Participants Surviving Following Hippocampal-sparing PCI
timeFrame: Up to 24 months post radiation treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kristin Redmond, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Redmond KJ, Hales RK, Anderson-Keightly H, Zhou XC, Kummerlowe M, Sair HI, Duhon M, Kleinberg L, Rosner GL, Vannorsdall T. Prospective Study of Hippocampal-Sparing Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017 Jul 1;98(3):603-611. doi: 10.1016/j.ijrobp.2017.03.009. Epub 2017 Mar 14.