Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer

Not Applicable

Completed

Conditions: Small Cell Lung Cancer Limited Stage
SCLC
Small-cell Lung Cancer

Interventions: Radiation: Hippocampal-sparing Prophylactic Cranial Irradiation

Registration Number: NCT01797159

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hippocampal-sparing PCI	Hippocampal-sparing Prophylactic Cranial Irradiation	Hippocampal-sparing PCI 25 Gy in 10 fractions

Primary Outcome Measures

Name	Time	Method
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	Baseline, 6 months and 12 months post radiation treatment	The primary endpoint of this study is cognitive function or memory. Memory is measured by participant performance on the Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R-Delayed Recall) at 6 months following hippocampal-sparing PCI. The HVLT-Delayed minimum and Maximum scores are 0-12. A higher score means a better outcome.

Secondary Outcome Measures

Name	Time	Method
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30	Baseline and 12 months post radiation treatment	Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: * Dyspnoea * Insomnia * Appetite * Constipation * Diarrhoea * Finances * Fatigue * Nausea/Vomiting * Pain * Physical Function * Role Function * Emotional Function * Cognitive Function * Social Function * Global QoL
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)	Baseline and 6 months post radiation treatment	Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: * Headaches * Seizures * Drowsy * Hair loss * Itching * Weakness * Bladder * Future Uncertainty * Visual Disorder * Motor Dysfunction * Communication Deficit
Percentage of Participants Surviving Following Hippocampal-sparing PCI	Up to 24 months post radiation treatment	To evaluate the survival rates of study participants following hippocampal-sparing PCI.
Compare Cognitive Function Following Sparing PCI to That of Standard PCI	12 months post radiation treatment	Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) * Total Recall (0-36) higher = better * Delayed Recall (0-12) higher = better * Discrimination (-12 to 12) higher = better Trail Making A \& B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) * Letter Word Fluency (0-120) higher = better * Category Word Fluency (0-120) higher = better * Verbal Fluency (0-240) higher = better Learning and Memory * Verbal Composite T score (mean = 100, standard deviation = 15), higher = better * Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30	Baseline and 6 months post radiation treatment	Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: * Dyspnoea * Insomnia * Appetite * Constipation * Diarrhoea * Finances * Fatigue * Nausea/Vomiting * Pain * Physical Function * Role Function * Emotional Function * Cognitive Function * Social Function * Global QoL
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).	Baseline and 12 months post radiation treatment	Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: * Headaches * Seizures * Drowsy * Hair loss * Itching * Weakness * Bladder * Future Uncertainty * Visual Disorder * Motor Dysfunction * Communication Deficit Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Scale Visual Disorder Scale Motor Dysfunction Scale Communication Deficit Scale
Number Participants With Hippocampus Brain Metastases Following Sparing PCI	12 months	The number of participants with brain metastases after sparing PCI treatment was assessed to be compared to two existing studies.
Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected	6 months, 12 months, 18 months and 24 months post radiation treatment	Determine whether development of leptomeningeal carcinomatosis following hippocampal-sparing PCI is higher than expected.

Trial Locations

Locations (2): The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, United States
Bayview Medical Center
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Baltimore, Maryland, United States