Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
Condition: Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Recurrence
Intervention: Erlotinib Hydrochloride; Laboratory Biomarker Analysis; Pemetrexed Disodium
Intervention description: Given PO; Correlative studies; Given IV
Intervention MeSH terms: Pemetrexed; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well pemetrexed disodium with or without erlotinib
      hydrochloride works in treating patients with stage IIIB-IV or recurrent non-small cell lung
      cancer. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. 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 with or without erlotinib hydrochloride in treating non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed advanced (stage IIIB with
             a malignant pleural effusion or stage IV disease) or recurrent nonsquamous NSCLC

          -  Patients must have at least one measurable disease per RECIST criteria; all sites of
             disease must be assessed within 4 weeks prior to registration

          -  Patient must have disease progression after one prior combinational chemotherapy
             and/or targeted therapy other than pemetrexed or an epidermal growth factor receptor
             (EGFR) ) tyrosine kinase inhibitor (TKI) (such as erlotinib, gefitinib, or a second
             generation EGFR TKI); prior monoclonal antibody against EGFR is allowed) for
             metastatic disease, or relapse while receiving adjuvant therapy, or within 12 months
             of completing adjuvant therapy

          -  All patients will be screened for brain metastasis within 6 weeks prior to
             registration; patients with treated and stable brain metastases must have been treated
             with surgery and/or radiation and are asymptomatic and are no longer taking
             corticosteroids

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky >= 60%

          -  Absolute neutrophil count >= 1,500/uL

          -  Hemoglobin >= 8.0 g/dL

          -  Platelets >= 100,000/uL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except in known
             hepatic metastasis, wherein may be =< 3.0 X ULN

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3.0 x institutional ULN, except in known hepatic metastasis, wherein may be =< 5.0
             X ULN

          -  Creatinine clearance >= 45 mL/min for patients with creatinine levels above
             institutional normal

          -  Patients must not be pregnant or breastfeeding since there is no information regarding
             the use of these agents in this population; a negative serum or urine pregnancy test
             is required within 14 days prior to registration if pre- or perimenopausal (i.e., last
             menstrual period within one year of registration); both pemetrexed and erlotinib are
             Class D agent with the potential for teratogenic or abortifacient effects; patients
             both females and males with reproductive potential (i.e. menopausal for less than 1
             year and not surgically sterilized) must practice contraceptive measures throughout
             the study

          -  Patients taking Warfarin or nonsteroidal anti-inflammatory drugs (NSAIDs) are
             eligible; patients with mild to moderate renal insufficiency should avoid taking
             NSAIDs with short elimination half-lives for a period of 2 days before, the day of,
             and 2 days following administration of Alimta; if the patient is taking other
             cytochrome P450 3A4 (CYP3A4) inducers or inhibitors, they must be discontinued at
             least one week prior to starting erlotinib

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had immunotherapy, hormone, chemotherapy or radiotherapy within 4
             weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those
             who have not recovered from adverse events due to agents administered more than 4
             weeks earlier

          -  Patients who have received pemetrexed or an EGFR TKI (such as erlotinib, gefitinib, or
             a second generation anti-EGFR TKI) for their metastatic disease should be excluded
             from this clinical trial; other molecularly targeted agent, including monoclonal
             antibody or vaccine against EGFR or angiogenesis inhibitor, is allowed

          -  Patients may not be receiving any other investigational or commercial agents or
             therapies other than those described below with the intent to treat the patient's
             malignancy

          -  Patients with uncontrolled brain metastases should be excluded from this clinical
             trial because of their poor prognosis

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to erlotinib or pemetrexed or other agents used in the study

          -  Patients with gastrointestinal tract disease resulting in an inability to take oral
             medication or a requirement for IV alimentation, prior surgical procedures affecting
             absorption, or active peptic ulcer disease, are ineligible

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection (such as bacteremia or active hepatitis), symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements

          -  Patients with immune deficiency are at increased risk of lethal infections when
             treated with marrow-suppressive therapy; therefore, human immunodeficiency virus
             (HIV)-positive patients receiving combination anti-retroviral therapy are excluded
             from the study because of possible pharmacokinetic interactions with erlotinib or
             pemetrexed or other agents administered during the study; appropriate studies will be
             undertake in patients receiving combination anti-retroviral therapy when indicated