Testing Whether Avoiding the Hippocampus During Whole-Brain Radiation Therapy Prevents Cognitive Side Effects in Patients with Small Cell Lung Cancer
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; * High-grade neuroendocrine carcinoma or combined SCLC and non-small cell lung cancer (NSCLC) is permitted
- Patients must be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy, Note: * Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration * For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted
- Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) magnetic resonance imaging (MRI) scan; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm; sites may contact the Imaging Co-Chairs for further information or assistance if needed * This MRI must be obtained within 56 days prior to Step 1 registration. * Note: the MRI study is mandatory irrespective of randomization to the experimental or control arm of this study
- 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 prior to initiating chemotherapy or thoracic radiotherapy) * MRI of the brain with contrast or diagnostic head CT with contrast * For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC
- After chemotherapy, patients must be restaged prior Step 1 registration using the same diagnostic work-up as required pre-chemotherapy; repeat PET/CT or bone scan is not required; patients must have: * History/physical examination within 30 days of Step 1 registration * No central nervous system (CNS) metastases (repeat MRI required) within 56 days prior to Step 1 registration * No progression in any site * Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration ** If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment ** Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression
- Zubrod performance status 0-2 within 30 days prior to Step 1 registration
- Women of childbearing potential must have a negative qualitative serum pregnancy test =< 14 days prior to Step 1 registration
- Patients who are primary English or French speakers are eligible
- Patients must sign a study-specific informed consent prior to study entry
- PRIOR TO STEP 2 REGISTRATION
- The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (parts A and B), 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, within 3 business days, a notification will be sent to the site to proceed to Step 2 registration; at minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible
- Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall. as determined by central assessment by the Neurocognitive Co-Chair, Dr. Wefel
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 or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
- Planned concurrent chemotherapy during PCI * Concurrent atezolizumab permitted
- 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 * Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter ** Note: patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to Step 1 registration ** Note: HIV testing is not required for eligibility for this protocol
- Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.
Alabama
Birmingham
Tuscaloosa
Arizona
Tucson
California
Greenbrae
Los Angeles
Merced
Oakland
Orange
Rancho Cordova
Roseville
Sacramento
San Francisco
Santa Clara
Truckee
Vallejo
Colorado
Englewood
Fort Collins
Connecticut
Bridgeport
New Haven
Delaware
Newark
Florida
Boca Raton
Coral Gables
Fort Lauderdale
Miami
Orlando
Tampa
Georgia
Atlanta
Cumming
Savannah
Hawaii
Aiea
Honolulu
Idaho
Boise
Caldwell
Meridian
Nampa
Twin Falls
Illinois
Chicago
Decatur
Effingham
Geneva
Hines
Libertyville
Maywood
Peoria
Springfield
Urbana
Warrenville
Indiana
Anderson
Fort Wayne
Goshen
Muncie
Iowa
Cedar Rapids
Des Moines
Kansas
Kansas City
Lawrence
Overland Park
Wichita
Kentucky
Lexington
Louisiana
New Orleans
Maryland
Annapolis
Baltimore
Bel Air
Columbia
Glen Burnie
Ocean Pines
Salisbury
Towson
Massachusetts
Burlington
Lowell
Worcester
Michigan
Ann Arbor
Bay City
Brighton
Brownstown
Chelsea
Clarkston
Clinton Township
Dearborn
Detroit
Farmington Hills
Flint
Grand Rapids
Kalamazoo
Lapeer
Livonia
Macomb
Mount Clemens
Mount Pleasant
Muskegon
Owosso
Petoskey
Pontiac
Port Huron
Royal Oak
Saint Joseph
Troy
West Bloomfield
Minnesota
Albert Lea
Duluth
Mankato
Minneapolis
Northfield
Rochester
Saint Louis Park
Missouri
Cape Girardeau
Creve Coeur
Joplin
Kansas City
North Kansas City
Saint Louis
Montana
Billings
Great Falls
Missoula
Nebraska
Omaha
Nevada
Reno
New Hampshire
Dover
Lebanon
New Jersey
Basking Ridge
Englewood
Middletown
Mount Holly
Voorhees
New Mexico
Albuquerque
New York
Bay Shore
Bronx
Brooklyn
Buffalo
Commack
Elmira
Lake Success
New York
Rochester
Staten Island
Syracuse
Uniondale
West Harrison
North Carolina
Charlotte
Concord
Monroe
Shelby
North Dakota
Bismarck
Fargo
Ohio
Akron
Chardon
Chillicothe
Cleveland
Columbus
Dayton
Elyria
Independence
Mentor
Middleburg Heights
Parma
Strongsville
Westlake
Wooster
Oklahoma
Oklahoma City
Oregon
Gresham
Portland
Pennsylvania
Abington
Broomall
Bryn Mawr
Chadds Ford
Danville
Dunmore
Gettysburg
Glen Mills
Lewisburg
Media
Philadelphia
Reading
West Reading
Wilkes-Barre
Wynnewood
York
South Carolina
Anderson
Boiling Springs
Greenville
Greenwood
Hilton Head Island
Lancaster
Rock Hill
South Dakota
Rapid City
Sioux Falls
Tennessee
Knoxville
Maryville
Nashville
Texas
Galveston
Houston
League City
Utah
Ogden
Salt Lake City
Vermont
Berlin
Burlington
Saint Johnsbury
Virginia
Richmond
West Virginia
Morgantown
Wheeling
Wisconsin
Antigo
Brookfield
Eau Claire
Franklin
Grafton
Green Bay
Johnson Creek
Kenosha
La Crosse
Madison
Menomonee Falls
Milwaukee
Oshkosh
Racine
Stevens Point
Summit
Two Rivers
Wausau
West Allis
Weston
Wisconsin Rapids
Ontario
Kingston
London
Newmarket
Ottawa
Toronto
Quebec
Montreal
Quebec City
Sherbrooke
Saskatchewan
Regina
Saskatoon
PRIMARY OBJECTIVES:
I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component [Non-Inferiority])
II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component [Efficacy])
SECONDARY OBJECTIVES:
I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association [COWA] test, and Trail Making Test [TMT] parts A and B), after PCI versus HA-PCI in SCLC.
II. 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.
III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-Core [C]30 and Brain Cancer Module [BN] 20) between PCI versus HA-PCI for patients with SCLC.
IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC.
V. 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.
VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria.
VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.
VIII. Assess cost-effectiveness of HA-PCI (modulated radiation therapy [MRT]) and PCI (3-dimensional conformal radiation therapy [3DCRT]) using the EuroQOL-5 dimension (D) health state classification (EQ-5D-5L).
IX. Correlate micro-ribonucleic acid (miRNA) signatures with cognitive failure in SCLC patients who received PCI and HA-PCI.
X. Evaluate APOE genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance.
XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.
EXPLORATORY OBJECTIVES:
I. Collect serum and whole blood for future translational research analyses.
II. Compare levels of hopefulness between PCI versus HA-PCI for patients with SCLC.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks.
ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks.
After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.
Trial Phase Phase II/III
Trial Type Supportive care
Lead Organization
NRG Oncology
Principal Investigator
Vinai Gondi
- Primary ID NRG-CC003
- Secondary IDs NCI-2015-01548
- Clinicaltrials.gov ID NCT02635009