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Completed

NCT Number: NCT01797159

Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer

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.

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Key information

Conditions

Small-cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms SCLC Small Cell Lung Cancer Limited Stage Small Cell Lung Carcinoma Thoracic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Bayview Medical Center, Baltimore, Maryland, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Hippocampal-sparing Prophylactic Cranial Irradiation

Radiation

Hippocampal-sparing Prophylactic Cranial Irradiation

Primary outcomes

  1. 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

    Time frame: 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 outcomes

  1. Compare Cognitive Function Following Sparing PCI to That of Standard PCI

    Time frame: Baseline

    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

  2. Compare Cognitive Function Following Sparing PCI to That of Standard PCI

    Time frame: 6 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

  3. Compare Cognitive Function Following Sparing PCI to That of Standard PCI

    Time frame: 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

  4. Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30

    Time frame: 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

  5. Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30

    Time frame: 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

  6. Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)

    Time frame: 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

  7. 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).

    Time frame: 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

  8. Number Participants With Hippocampus Brain Metastases Following Sparing PCI

    Time frame: 12 months

    The number of participants with brain metastases after sparing PCI treatment was assessed to be compared to two existing studies.

  9. Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected

    Time frame: 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.

  10. Percentage of Participants Surviving Following Hippocampal-sparing PCI

    Time frame: Up to 24 months post radiation treatment

    To evaluate the survival rates of study participants following hippocampal-sparing PCI.

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2018
Study completion
2019
First posted
Feb 22, 2013
Registry last updated
Oct 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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