RTOG 1306 A RANDOMIZED PHASE II STUDY OF INDIVIDUALIZED COMBINED MODALITY THERAPY FOR STAGE III NON-SMALL CELL LUNG CANCER (NSCLC)

Summary

institution's Screening for Biomarkers Prior to Randomization: Mandatory
The enrolling institution is responsible for screening for documentation of eGFR TK mutation and eML4-aLK fusion arrangement.

eGFR TK Mutation Cohort. Patient will be randomized to
arm 1 erlotinib, 150 mg/day for 12 weeks (four 3-week cycles), then radiation therapy and chemotherapy.
arm 2 standard radiation therapy and chemotherapy

eML4-aLK fusion arrangement cohort. Patient will be randomized to
arm 3 Crizotinib, 250 mg/ twice a day for 12 weeks (four 3-week cycles), then radiation therapy and chemotherapy
arm 4 standard radiation therapy and chemotherapy

Patients with both the eGFR mutation and aLK arrangement will be placed in the aLK
Cohort.

all patients must consent to pre-entry biomarker screening of tissue for eGFR mutation analysis and aLK fusion arrangement by the enrolling institution (must be done in a CLia certified lab). The institution must provide the following material to the RToG Biospecimen Resource for retrospective central review of biomarker screening within 42 calendar days of enrolling the patient: (1) one H and e stained slide per positive biopsy site (slide can be a duplicate cut stained H [and] e; it does not have to be the diagnostic slide, (2) 5 micron unstained sections cut onto positive charged slides; The slides must be clearly labeled with the pathology identification number that corresponds to the Pathology Report and the block id; (3) a Pathology Report documenting that the submitted slides contain tumor; the report must include the RToG protocol number and the patient's case number; (4) a Specimen Transmittal (ST) Form stating that the tissue is being submitted for central review and biomarker analysis.

Participant Eligibility

1. Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC;
2. Unresectable stage IIIA or IIIB disease; patients must be surgically staged to confirm N2 or N3
disease. Patients may have invasive mediastinal staging by mediastinoscopy, mediastinotomy,
EBUS-TBNA, EUS, or VATS within 30 days prior to registration.
3. Patients with any T with N2 or N3 are eligible. Patients with T3, N1-N3 disease are eligible if
deemed unresectable. Patients with T4, any N are eligible.
4. Patients must have measurable disease, i.e., lesions that can be accurately measured in at least
1 dimension (longest dimension in the plane of measurement is to be recorded) with a minimum
size of 10 mm by CT scan (CT scan slice thickness no greater than 5 mm). Tumor measurements
must be taken within 42 days prior to registration.
5. Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are
eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field
of radiotherapy.
6. If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too small to tap,
the patient will be eligible. Patients who develop a new pleural effusion after thoracotomy or other
invasive thoracic procedure will be eligible.
7. The institution[Single Quote]s pre-enrollment biomarker screening at a CLIA certified lab documents presence
of known
* sensitive
* mutations in EGFR TK domain (exon 19 deletion, L858) and EML4- ALK
fusion arrangement. Either the primary tumor or the metastatic lymph node tissue may be used
for testing of mutations.
8. The institution[Single Quote]s pre-enrollment biomarker screening at a CLIA certified lab documents absence of
T790M mutation in the EGFR TK domain;
9. Appropriate stage for protocol entry, including no distant metastases, based upon the following
minimum diagnostic workup:

* History/physical examination, including recording of pulse, BP, weight, and body surface
area, within 45 days prior to registration;

* Whole body FDG-PET/CT (orbits to mid-thighs) within 30 days prior to registration; PET/CT
must be negative for distant metastasis.

* CT scan of the chest with contrast (unless medically contraindicated) within 30 days prior to
registration;

* MRI of the brain with contrast (or CT scan with contrast, if MRI medically contraindicated)
within 30 days prior to registration.
10. Zubrod Performance Status 0-1 within 14 days prior to registration;
11. Age >= 18;
12. CBC/differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows:
Absolute neutrophil count (ANC) >= 1,500 cells/mm3;

* Platelets >= 100,000 cells/mm3;

* Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
8.0 g/dl is acceptable.);
13. Adequate renal and hepatic function, defined as follows:

* Calculated Creatinine Clearance >= 50 ml/min (by Cockroft-Gault formula) within 14 days
prior to registration;

* AST/ALT < 3 X ULN within 14 days prior to registration;

* Bilirubin < 3 X ULN within 14 days prior to registration
14. Negative serum pregnancy test within 14 days prior to registration for women of childbearing
potential;
15. Patient must provide study specific informed consent prior to study entry, including consent for
mandatory screening of tissue.