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 nRG oncology Biospecimen Bank 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

3.1.1 Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC;
3.1.2 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.
3.1.3 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.
3.1.4 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.
3.1.5 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.
3.1.6 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.
3.1.7 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/or EML4-
ALK fusion arrangement. Either the primary tumor or the metastatic lymph node tissue may be
used for testing of mutations.
3.1.8 The institution[Single Quote]s pre-enrollment biomarker screening at a CLIA certified lab documents absence of
T790M mutation in the EGFR TK domain;
3.1.9 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.
3.1.10 Zubrod Performance Status 0-1 within 14 days prior to registration;
3.1.11 Age >= 18;
3.1.12 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.);
3.1.13 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 <= 2.5 X ULN within 14 days prior to registration;

* Bilirubin within normal institutional limits within 14 days prior to registration
3.1.14 Negative serum pregnancy test within 14 days prior to registration for women of childbearing
potential;
3.1.15 Patient must provide study specific informed consent prior to study entry, including consent for
mandatory screening of tissue.