Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer

"A Phase II Trial of Hippocampal-Sparing Cranial Irradiation (PCI) for Small-Cell Lung Cancer (SCLC)"

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.

Study Overview

• Status: Completed
• Conditions: SCLC; Small-cell Lung Cancer; Small Cell Lung Cancer Limited Stage
• Intervention / Treatment: Radiation: Hippocampal-sparing Prophylactic Cranial Irradiation

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21227
      • Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hippocampal-sparing PCI; Hippocampal-sparing PCI 25 Gy in 10 fractions	Radiation: Hippocampal-sparing Prophylactic Cranial Irradiation; Hippocampal-sparing Prophylactic Cranial Irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline, 6 months and 12 months post radiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Cognitive Function Following Sparing PCI to That of Standard PCI	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	Baseline
Compare Cognitive Function Following Sparing PCI to That of Standard PCI	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	6 months post radiation treatment
Compare Cognitive Function Following Sparing PCI to That of Standard PCI	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	12 months post radiation treatment
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30	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	Baseline and 6 months post radiation treatment
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30	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	Baseline and 12 months post radiation treatment
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)	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	Baseline and 6 months post radiation treatment
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).	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	Baseline and 12 months post radiation treatment
Number Participants With Hippocampus Brain Metastases Following Sparing PCI	The number of participants with brain metastases after sparing PCI treatment was assessed to be compared to two existing studies.	12 months
Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected	Determine whether development of leptomeningeal carcinomatosis following hippocampal-sparing PCI is higher than expected.	6 months, 12 months, 18 months and 24 months post radiation treatment
Percentage of Participants Surviving Following Hippocampal-sparing PCI	To evaluate the survival rates of study participants following hippocampal-sparing PCI.	Up to 24 months post radiation treatment

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 11, 2013
• Primary Completion (ACTUAL): March 18, 2018
• Study Completion (ACTUAL): March 18, 2019

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (ESTIMATE): February 22, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: PCI; Prophylactic Cranial Irradiation; Hippocampal-sparing irradiation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: J12127; NA_00078659 (OTHER: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share data with PIs who are not included on the study team.