Clinical trial NCT00738881 (phase 3, status: terminated)
Conditions: recurrent non-small cell lung carcinoma, stage iiia non-small cell lung cancer, stage iiib non-small cell lung cancer, stage iv non-small cell lung cancer
ICD codes: D02.20, D02.21, D02.22, C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2, C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2, C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: erlotinib hydrochloride, pemetrexed disodium
SMILES: COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2, [H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(CCC2=CNC3=C2C(O)=NC(=N)N3)C=C1)C(O)=O
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Documented recurrence or disease progression of NSCLC

               -  NSCLC must be confirmed by pathologic examination, either on initial diagnosis or
                  disease recurrence/progression; mixed histology allowed if all components
                  consistent with NSCLC

          -  Measurable disease, defined as at least one lesion whose longest diameter can be
             accurately measured as >= 2.0 cm by conventional techniques or as >= 1.0 cm by spiral
             computed tomography (CT); if spiral CT is used, it must be used for both pre- and
             post- treatment tumor assessments

          -  Prior radiation therapy is permitted as long as:

               -  Recovered from the toxic effects of radiation treatment before study entry,
                  except for alopecia

               -  =< 25% of bone marrow radiated

               -  Presence of measurable disease whether in-field disease progression/recurrence or
                  disease outside the treatment fields of radiation port

          -  Absolute neutrophil count (ANC) >= 1,500 uL

          -  Platelet (PLT) >= 100,000 uL

          -  Hemoglobin (Hgb) >= 10 g/dL

          -  Total bilirubin: within normal institutional limits (WNL) OR direct bilirubin =< upper
             limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

          -  International normalized ratio (INR) =< 1.5

          -  Calculated creatinine clearance >= 45 mL/min using the Cockcroft-Gault formula

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  Negative pregnancy test done =< 7 days prior to pre-registration, for women of
             childbearing potential only

          -  Ability to provide informed consent

          -  Life expectancy >= 12 weeks

          -  Tissue available and willing to submit tissue for central pathology review and EGFR
             evaluation; performed on original diagnostic/recurrent tissue (preferably
             paraffin-embedded tissue blocks); if institution unable to release tissue blocks,
             willing to submit 25 unstained slides (15 sections cut at 5 microns mounted on charged
             slides and 10 sections cut at 10 microns mounted on uncharged slides)

          -  Must be previously treated for advanced disease with only 1 chemotherapy regimen which
             must contain cytotoxic agent(s); adjuvant/neoadjuvant treatment with cytotoxic
             agent(s) administered < 12 months (from date chemotherapy was started) prior to
             pre-registration will be considered as one prior treatment; NOTE: adjuvant/neoadjuvant
             treatment administered >= 12 months, use of targeted agents such as monoclonal
             antibodies prior to pre-registration will NOT be counted as one prior treatment;
             patient could have had adjuvant/neoadjuvant chemotherapy >= 12 months and 1 systemic
             chemotherapy regimen for metastatic or recurrent disease

          -  Able to take folic acid, vitamin B12 supplementation, and dexamethasone

          -  Able to permanently discontinue aspirin dose of >= 1.3 grams/day >= 10 days before and
             after pemetrexed treatment

          -  Fertile patients must use effective contraception

          -  Able to take folic acid, vitamin B_12 supplementation, and dexamethasone

          -  Stable brain metastasis that have been treated with either whole brain radiation
             therapy or gamma knife surgery and are off steroid treatment for > 14 days prior to
             pre-registration, if applicable

          -  Willingness to return to enrolling institution for treatment and follow-up

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Any clinically significant infection, at the treating physician's discretion

          -  Known human immunodeficiency virus (HIV) positive patients

          -  Impairment of gastrointestinal (GI) function, inability to swallow pills in the
             absence of a feeding tube, or GI disease that may significantly alter absorption of
             oral medications (e.g. ulcerative disease, uncontrolled nausea and vomiting,
             malabsorption syndromes, bowel obstruction, etc)

          -  Serious condition that, in the opinion of the investigator, would compromise the
             patient's ability to complete the study or increase the risk for serious adverse
             events

          -  Any of the following prior therapies:

               -  Prior radiation to > 25% of bone marrow

               -  EGFR tyrosine kinase inhibitors

               -  Pemetrexed

               -  Chemotherapy =< 3 weeks prior to pre-registration

               -  Mitomycin C/nitrosoureas =< 6 weeks prior to pre-registration

               -  Immunotherapy =< 2 weeks prior to pre-registration

               -  Biologic therapy =< 2 weeks prior to pre-registration

               -  Gene therapy =< 2 weeks prior to pre-registration

               -  Full field radiation therapy =< 4 weeks prior to pre-registration

               -  Limited field radiation therapy =< 2 weeks prior to pre-registration

               -  Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =<
                  4 weeks prior to pre-registration or anticipation of need for major surgical
                  procedure during the course of the study; minor surgery =< 2 weeks prior to
                  pre-registration; insertion of a vascular access device is not considered major
                  or minor surgery in this regard

          -  Other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary
             therapy considered investigational (utilized for a non-Food and Drug Administration
             [FDA]-approved indication and in the context of a research investigation) =< 4 weeks
             prior to pre-registration

          -  Steroid therapy for brain metastasis =< 14 days prior to pre-registration

          -  Symptomatic serosal effusion (>= Common Terminology Criteria for Adverse Events
             [CTCAE] v3.0 grade 2 dyspnea) that is not amenable to drainage prior to
             pre-registration

          -  Other invasive solid or hematologic malignancy; exceptions: prior malignancy was
             diagnosed and definitively treated >= 5 years previously with no subsequent evidence
             of recurrence; patients with a history of low-grade (Gleason score =< 6) localized
             prostate cancer will be eligible even if diagnosed < 3 years prior to
             pre-registration; these patients may continue on medications concomitantly to maintain
             their disease remission as necessary; patients with carcinoma in situ, regardless of
             organ involvement, or non-melanoma cutaneous carcinomas are eligible if these were
             definitively treated >= 3 years previously with no subsequent evidence of recurrence;
             Note: patients with breast cancer that was definitively treated > 5 years earlier but
             continue to receive aromatase inhibitors are NOT eligible

          -  Only non-measurable disease, defined as all other lesions, including small lesions
             whose longest diameter measures < 2 cm with conventional techniques or < 1.0 cm with
             spiral CT, and truly non-measurable lesions, which include the following as per
             Response Evaluation Criteria In Solid Tumors (RECIST) criteria dated June 1999:

               -  Bone lesions

               -  Leptomeningeal disease

               -  Ascites

               -  Pleural/pericardial effusion

               -  Inflammatory breast disease

               -  Lymphangitis cutis/pulmonis

               -  Abdominal masses that are not confirmed and followed by imaging techniques

               -  Cystic lesions

               -  Single disease site in prior radiation field

          -  Any of the following concurrent severe and/or uncontrolled medical conditions:

               -  Angina pectoris

               -  History of congestive heart failure =< 3 months prior to pre-registration, unless
                  ejection fraction > 40%

               -  Myocardial infarction =< 6 months prior to pre-registration

               -  Cardiac arrhythmia

               -  Diabetes mellitus

               -  Hypertension

               -  Any other severe underlying diseases which are, in the judgment of the
                  investigator, inappropriate for entry into this study

          -  Respiratory symptoms > CTCAE grade 1