Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer
Condition: 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
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib Hydrochloride; Pemetrexed Disodium
Intervention description: Given PO; Given IV
Intervention MeSH terms: Pemetrexed; Erlotinib Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies pemetrexed disodium to see how well it works compared
      with erlotinib hydrochloride as second-line therapy in treating patients with non-small cell
      lung cancer that has spread to other places in the body. Pemetrexed disodium and erlotinib
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth. It is not yet known whether pemetrexed disodium is more effective than erlotinib
      hydrochloride in treating advanced non-small cell lung cancer.
    

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