Details

Details

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

IRB NRG-CC003

CC 16-553

Hospital Fairview, Main Campus, Strongsville, Wooster

Stage Stage 1, Stage 2, Stage 3, Stage 4

Phase Phase 2, Phase 3

Disease Lung - SCLC (Small-Cell Lung Cancer), Lung - SCLC (Small-Cell Lung Cancer)

Drug Memantine

Description

Description

Primary Objective
  • 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.
  • 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 Objective
  • 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.
  • 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.
  • 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.
  • Compare overall survival after PCI versus HA-PCI for patients with SCLC.
  • 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.
  • Evaluate adverse events according to CTCAE criteria.
  • Correlate changes in HRQOL domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.
  • Assess cost-effectiveness of HA-PCI (MRT) and PCI (3DCRT) using the EQ-5D-5L.
  • Correlate miRNA signatures with cognitive failure in SCLC patients who received PCIand HA-PCI
  • Evaluate APOE genotyping as potential predictor of neurocognitive decline, hippocampalatrophy after brain irradiation and/or differential benefit from hippocampal avoidance.
  • Evaluate baseline MR imaging biomarkers of white matter injury and hippocampalvolumetry as potential predictors of cognitive decline and differential benefit from HAPCIas compared to PCI.
Inclusion Criteria

Inclusion Criteria

Prior to Step 1 Registration
  1. Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration;
  2. Patients must be registered on study no earlier than 7 days and no later than 56 days prior to Step 1 registration after completing chemotherapy (+/- thoracic radiotherapy).
  3. 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 fluidattenuation inversion recovery (FLAIR) sequence acquisitions within 56 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. Vendor-specific versions of this sequence are available for download from the ADNI website, http://www.adniinfo.org/scientists/MRIProtocols.aspx. 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 acan be up to 2.5 mm in slice thickness. This imaging is considered standard of care. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study.
  4. Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following:
    • History/physical examination;
    • CT of the chest and abdomen with contrast (does not have to be done if the patient has had a PET/CT scan prior to initiating chemotherapy or thoracic radiotherapy);
    • MRI of the brain prior to initiating chemotherapy or thoracic radiotherapy;
    • 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.
  5. After chemotherapy, patients must be restaged within 56 days prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy (see Section 3.2.4). Repeat PET/CT or bone scan is not required. Patients must have:
    • History/physical examination;
    • No CNS metastases (Repeat MRI required; see Section 3.2.3 for details);
    • Radiographic partial or complete response to chemotherapy in at least one disease site using RECIST criteria;
    • No progression in any site.
  6. Zubrod performance status 0-2 within 30 days prior to Step 1 registration;
  7. Age ≥ 18;
  8. Women of childbearing potential must have a negative qualitative serum pregnancy test ≤ 14 days prior to Step 1 registration.
  9. Patients who are primary English or French speakers are eligible.
  10. Patients must sign a study-specific informed consent prior to study entry.
Prior to Step 2 Registration
  1. The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after Step 1 registration: HVLT-R, TMT, and COWA. The neurocognitive assessments will be uploaded into the 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.
  2. Patients must have a baseline raw score greater than 2 on the HVLT-R Delayed Recall to be determined by the Neurocognitive Co-Chair, Dr. Wefel.
Exclusion Criteria

Exclusion Criteria

Patients with any of the following conditions are NOT eligible for this study.

  1. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields;
  2. Radiographic evidence of CNS metastases;
  3. Radiographic evidence of hydrocephalus;
  4. Planned concurrent chemotherapy or anti-tumor agent during PCI;
  5. 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.
  6. Contraindiction to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia;
  7. 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;
    • HIV positive with CD4 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 ≥ cells/microliter within 30 days prior to Step 1 registration.
      • Note: HIV testing is not required for eligibility for this protocol.
  8. 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.