Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer
Condition: Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Radiation Therapy; Carboplatin; Cisplatin; Crizotinib; Erlotinib; Etoposide; Paclitaxel
Intervention description: 30 once-daily 2 Gy fractions over 6 weeks totaling 60 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT).; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable.
Consolidation: 4-6 weeks after completion of RT, AUC=6, IV, days 1 and 22.; 50 mg/m2, IV (intravenous), on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, cisplatin will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; 250 mg, orally, twice daily for four 3-week cycles (12 weeks in total); 150 mg, orally, once daily for four 3-week cycles (12 weeks in total); 50 mg/m2, IV, on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, etoposide will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable.
Consolidation: 4-6 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.
Intervention MeSH terms: Paclitaxel; Etoposide; Podophyllotoxin; Cisplatin; Carboplatin; Albumin-Bound Paclitaxel; Etoposide phosphate; Erlotinib Hydrochloride; Crizotinib; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with
      chemoradiation therapy works in treating patients with stage III non-small cell lung cancer.
      Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy
      that delivers a high dose of radiation directly to the tumor may kill more tumor cells and
      cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide,
      paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either
      by killing the cells, by stopping them from dividing, or by stopping them from spreading. It
      is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib
      with chemoradiation therapy in treating patients with non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC

          -  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, endobronchial ultrasound transbronchial aspiration (EBUS-TBNA),
             endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery (VATS)

          -  Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3, N1-N3
             disease are eligible if deemed unresectable; patients with T4, any N are eligible

          -  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 computed tomography (CT) scan (CT scan slice
             thickness no greater than 5 mm)

          -  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

          -  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

          -  The institution's pre-enrollment biomarker screening at a Clinical Laboratory
             Improvement Amendments (CLIA) certified lab documents presence of known "sensitive"
             mutations in epidermal growth factor receptor tyrosine kinase (EGFR TK) domain (exon
             19 deletion, L858) and/or EML4-anaplastic lymphoma kinase (ALK) fusion arrangement;
             either the primary tumor or the metastatic lymph node tissue may be used for testing
             of mutations

          -  The institution's pre-enrollment biomarker screening at a CLIA certified lab documents
             absence of T790M mutation in the EGFR TK domain

          -  Appropriate stage for protocol entry, including no distant metastases, based upon the
             following minimum diagnostic workup:

               -  History/physical examination, including recording of pulse, blood pressure (BP),
                  weight, and body surface area, within 45 days prior to registration

               -  Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to
                  mid-thighs) within 30 days prior to registration; PET/CT must be negative for
                  distant metastasis

               -  CT scan with contrast of the chest and upper abdomen to include liver and
                  adrenals (unless medically contraindicated) within 30 days prior to registration

               -  Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with
                  contrast, if MRI medically contraindicated) within 30 days prior to registration

          -  Zubrod performance status 0-1 within 14 days prior to registration

          -  Absolute neutrophil count (ANC) >= 1,000 cells/mm^3

          -  Platelets >= 100,000 cells/mm^3

          -  Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve
             hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

          -  Serum creatinine < 1.5 mg/dL or calculated creatinine clearance >= 50 ml/min (by
             Cockcroft-Gault formula) within 14 days prior to registration

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
             of normal (ULN) within 14 days prior to registration

          -  Bilirubin within normal institutional limits within 14 days prior to registration

          -  Negative serum pregnancy test within 14 days prior to registration for women of
             childbearing potential

          -  Patient must provide study specific informed consent prior to study entry, including
             consent for mandatory screening of tissue

        Exclusion Criteria:

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 730 days (2 years) (for example, carcinoma in situ of the breast,
             oral cavity, or cervix are all permissible)

          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
             different cancer is allowable

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          -  Atelectasis of the entire lung

          -  Contralateral hilar node involvement

          -  Exudative, bloody, or cytologically malignant effusions

          -  Severe, active co-morbidity, 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

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of
                  registration; hepatic insufficiency resulting in clinical jaundice and/or
                  coagulation defects

               -  Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
                  Control and Prevention (CDC) definition; note, however, that human
                  immunodeficiency virus (HIV) testing is not required for entry into this
                  protocol; protocol-specific requirements may also exclude immuno-compromised
                  patients

          -  Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception

          -  Prior allergic reaction to the study drug(s) involved in this protocol