Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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.
Phase
Phase 2/Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Thoracic Oncology
Enrollment Eligibility
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 NSCLC is permitted.
- Patients must have received chemotherapy and 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) MRI scan (see section 11.3 regarding axial T2/FLAIR sequence). 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 +/- thoracic radiotherapy, patients must be defined as
limited-stage or extensive-stage SCLC after clinical staging evaluation involving the
following:
1. History/physical examination;
2. 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);
3. MRI of the brain with contrast or diagnostic head CT with contrast;
4. 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 to 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 CNS metastases (Repeat MRI required; see Section 3.2.3 for details) 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.
1. 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.
2. 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
- 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
- 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 NRG Oncology RAVE System for evaluation by Dr.
Wefel. Once the upload is complete, within 3 business days, a notification email 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
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 or anti-tumor agent 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
- HIV positive with CD4 count < 200 cells/microliter;
1. 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.
2. 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