Clinical Trial 18555

Cancer Type: Thoracic
Interventions:

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:


    Overview

    Study Title

    A Randomized Phase II/III Trial of Prophylactic Cranial Irradiation with or without Hippocampal Avoidance for Small Cell Lung Cancer

    Summary

    The purpose of this study is to compare any good and bad effects of avoiding the hippocampus during whole-brain radiation to the usual whole-brain radiation. The first portion of this study will test if avoiding the hippocampus during whole-brain radiation is as effective as the usual treatment (whole-brain radiation) in decreasing the chance of cancer spreading to the brain. The second portion of the study will test if hippocampal avoidance decreases memory and thinking side effects.

    Objective

    Primary Objectives: 1. Randomized Phase II Component (Non-Inferiority): Determine whether the 12-month intracranial relapse rate following HA-PCI is non-inferior compared to the rate following PCI for patients with SCLC. 2. Phase III Component (Efficacy): Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in HVLT-R delayed recall compared to PCI for patients with SCLC. Secondary Objectives: 1. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, COWA test, and TMT Parts A and B), after PCI versus HA-PCI in SCLC. 2. 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 for SCLC. 3. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the EORTC QLQ-C30 and BN20) between PCI versus HA-PCI for patients with SCLC. 4. Compare overall survival after PCI versus HA-PCI for patients with SCLC. 5. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC. 6. Evaluate adverse events according to CTCAE criteria. 7. Correlate changes in HRQOL domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC. 8. Assess cost-effectiveness of HA-PCI (MRT) and PCI (3DCRT) using the EQ-5D-5L. Exploratory Objectives: 1. Collect serum and whole blood for future translational research analyses. 2. Evaluate baseline 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. 3. Compare levels of hopefulness between PCI versus HA-PCI for patients with SCLC.

    Inclusion Criteria

  • PRIOR TO STEP 1 REGISTRATION:
  • Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration
  • Participants must have a three-dimensional (3D), T1-weighted, spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan without and with gadolinium contrast-enhanced T1-weighted axial, coronal, and sagittal sequence acquisitions and standard T2-weighted axial and coronal fluid attenuation inversion recovery (FLAIR) sequence acquisitions within 28 days of Step 1 registration; to yield acceptable image quality, the pre-contrast-enhanced should have a resolution of 1 x 1 x 1.2 mm and should follow the protocols established by the Alzheimer's Disease Neuroimaging Initiative (ADNI); performance of this sequence at a 3 Tesla field strength is recommended; sites may contact the Imaging Co-Chair, Dr. Tammie Benzinger, for further information or assistance if needed; to yield acceptable image quality, the gadolinium contrast-enhanced T1-weighted scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the associated coronal and sagittal sequences can be up to 2.5 mm in slice thickness; this imaging is considered standard of care
  • Note: The MRI study as part of response assessment following chemotherapy can be used for this purpose, but the appropriate sequences must be obtained; this sequence cannot be obtained prior to chemotherapy and is mandatory irrespective of randomization to the experimental or control arm of this study
  • Must sign a study-specific informed consent prior to study entry
  • PRIOR TO STEP 2 REGISTRATION:
  • The following baseline neurocognitive assessments must be completed within 14 days prior to Step 2 registration: HVLT-R, TMT, and COWA; the neurocognitive assessments will be uploaded into the National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, and Gynecologic Oncology Group (NRG) Oncology RAVE system for evaluation by Dr. Wefel; once the upload is complete, a notification will be sent to the site to proceed to Step 2; NOTE: completed baseline neurocognitive assessments can be uploaded at the time of Step 1 registration
  • Participants must have a baseline raw score greater than 2 on the HVLT-R delayed recall
  • Prior to chemotherapy or thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following: History/physical examination; Computed tomography (CT) of the chest and abdomen with contrast (does not have to be done if the patient has had a positron emission tomography (PET)/CT scan within 8 weeks prior to initiating chemotherapy or thoracic radiotherapy); MRI of the brain; For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI, a PET/CT or bone scan is required to confirm limited-stage SCLC
  • Must be registered on study no earlier than 1 week and no later than 8 weeks after completing chemotherapy (+/- thoracic radiotherapy)
  • After chemotherapy, participants must be restaged using the same diagnostic work-up as required pre-chemotherapy; repeat PET/CT or bone scan is not required; patients must have: No central nervous system (CNS) metastases; Radiographic partial or complete response to chemotherapy in at least one disease site using Response Evaluation Criteria in Solid Tumors (RECIST) criteria; No progression in any site
  • Zubrod performance status 0-2
  • Women of childbearing potential and male participants must practice adequate contraception
  • Women of childbearing potential must have a negative qualitative serum pregnancy test => Primary English or French speakers are eligible

  • Exclusion Criteria

  • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
  • Radiographic evidence of CNS metastases
  • Radiographic evidence of hydrocephalus
  • Planned concurrent chemotherapy or anti-tumor agent during PCI
  • Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted
  • Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia
  • Severe, active comorbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Uncontrolled, clinically significant cardiac arrhythmias
  • Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception