Summary

for people ages 18 years and up (full criteria)
at UC Davis
study started
estimated completion:

Description

Summary

This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.

Official Title

Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer

Details

PRIMARY OBJECTIVES:

  1. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared 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:

  1. 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 BN20) 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 (intensity modulated radiation therapy [IMRT]) and PCI (3-dimensional conformal radiation therapy [3DCRT]) using the EuroQual (EQ)-5-Dimensions (5D)-5L.

TERTIARY OBJECTIVES:

  1. Collect serum, whole blood, and urine for future translational research analyses.

II. Evaluate baseline magnetic resonance (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.

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.

Keywords

Extensive Stage Small Cell Lung Carcinoma Limited Stage Small Cell Lung Carcinoma Carcinoma Small Cell Lung Carcinoma Lung Neoplasms 3-Dimensional Conformal Radiation Therapy Cognitive Assessment Intensity-Modulated Radiation Therapy Laboratory Biomarker Analysis Quality-of-Life Assessment

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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
  • Patients 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
  • 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 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
  • Patients 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
  • Patients must be registered on study no earlier than 1 week and no later than 8 weeks after completing chemotherapy (+/- thoracic radiotherapy)
  • After chemotherapy, patients 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=< 2 weeks prior to study entry
  • Patients who are primary English or French speakers are eligible

You CAN'T join if...

  • 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

Locations

  • University of California Davis Comprehensive Cancer Center currently not accepting new patients, but might later
    Sacramento California 95817 United States
  • California Pacific Medical Center-Pacific Campus currently not accepting new patients, but might later
    San Francisco California 94115 United States
  • Saint Joseph Hospital - Orange currently not accepting new patients, but might later
    Orange California 92868 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
NRG Oncology
ID
NCT02635009
Phase
Phase 2/3
Study Type
Interventional
Last Updated