Clinical trial NCT02134886 (phase 1, status: terminated)
Conditions: hiv infection, 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: Z21, 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
SMILES: COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2
Reason stopped: 
    no accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have known HIV infection and histologically confirmed non-small cell
             lung cancer that is metastatic or unresectable; patients will be eligible regardless
             of tumor EGFR mutation status

          -  Participants may have received any number of prior lines of chemotherapy (other than
             erlotinib or other EGFR-targeted therapy) for incurable non-small cell lung cancer;
             (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy
             counts as one line of therapy; prior adjuvant chemotherapy for early stage disease
             does not count as one line of therapy if 12 months or greater elapsed between
             completion of adjuvant therapy and initiation of first-line systemic therapy; if less
             than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy)

               -  PARTICIPANTS WITH NO PRIOR THERAPY FOR INCURABLE LUNG CANCER: trial eligibility
                  will be restricted to those participants whose tumors harbor known EGFR
                  activating mutations

               -  PARTICIPANTS WITH PRIOR LINES OF THERAPY: all other participants (those whose
                  tumors harbor wild-type EGFR or unknown EGFR status, or those with EGFR mutations
                  not previously treated with erlotinib/EGFR-targeted therapy)

               -  At least 4 weeks must have elapsed since prior chemotherapy or biological
                  therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior
                  radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at
                  least 3 months prior to registration; radiotherapy to any other site (including
                  bone or brain metastases) must be completed at least 28 days prior to
                  registration

          -  Molecular characterization of non-squamous non-small cell lung cancer will be
             recommended prior to enrollment per standard of care/institutional guidelines;
             consistent with current National Comprehensive Cancer Network (NCCN) guidelines and
             the recent Food and Drug Administration (FDA)-approval indication of erlotinib for
             first-line treatment of advanced non-small cell lung cancer in persons with tumor EGFR
             mutations, participants who have known EGFR sensitizing mutations in tumors will be
             permitted to enter the study and receive erlotinib as initial monotherapy; for
             participants who have received one or more prior lines of chemotherapy, molecular
             characterization of tumors is required whenever possible with an understanding that
             inability to obtain sufficient tissue specimen for characterization will not preclude
             enrollment into the study

          -  Participants must have measurable disease as defined by Response Evaluation Criteria
             in Solid Tumors (RECIST) version 1.1 criteria; baseline measurements and evaluation of
             ALL sites of disease must be obtained within 4 weeks prior to registration

          -  Serologic documentation of HIV infection at any time prior to study entry, as
             evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western
             blot, or any other federally approved licensed HIV test; alternatively, this
             documentation may include a record that another physician has documented that the
             participant has HIV infection based on prior ELISA and Western blot, or other approved
             diagnostic tests

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Life expectancy of greater than 12 weeks

          -  Leukocytes: >= 3,000/mm^3

          -  Absolute neutrophil count: >= 1,500/mm^3

          -  Platelets: >= 100,000/mm^3

          -  Total bilirubin: within normal institutional limits; if, however, the participant has
             Gilbert's disease or unconjugated hyperbilirubinemia which is felt to be secondary to
             with atazanavir or indinavir therapy, then the total bilirubin must be =< 3 x upper
             limit of normal [ULN])

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =<2.5 x
             institutional upper limit of normal

          -  Hemoglobin: >= 9 g/dL

          -  Creatinine:

               -  Creatinine levels within normal institutional limits (< 1.5 x ULN); or,

               -  Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine
                  levels above institutional normal

          -  A cluster of differentiation (CD)4+ lymphocyte count > 50/mcL will be required within
             2 weeks of study participation

          -  Women of childbearing potential must have a negative pregnancy test within 7 days of
             enrollment; women of childbearing potential include women who have experienced
             menarche and who have not undergone successful surgical sterilization (hysterectomy,
             bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal;
             postmenopause is defined as amenorrhea >= 12 consecutive months; note: women who have
             been amenorrheic for 12 or more months are still considered to be of childbearing
             potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens,
             ovarian suppression, or any other reversible reason

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately; men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of erlotinib administration

          -  Participants MUST receive appropriate care and treatment for HIV infection, including
             antiretroviral medications, when clinically indicated and should be under the care of
             a physician experienced in HIV management; participants will be eligible regardless of
             antiretroviral medication (including no antiretroviral medication) provided there is
             no intention to initiate therapy or the regimen has been stable for at least 4 weeks
             with no intention to change the regimen within 8 weeks following study entry; as
             study-specific (antiretroviral-based) strata fill, however, only participants who are
             receiving the therapies eligible for the remaining open strata will be accrued

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Participants who received prior treatment with erlotinib or other EGFR-targeted agents

          -  Participants who have had chemotherapy or radiotherapy within 4 weeks prior to
             entering the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier

          -  Participants who are receiving any other investigational agents

          -  The participant has active brain metastases or epidural disease; participants with
             stable brain metastases previously treated with whole brain radiation or radiosurgery
             or participants with epidural disease previously treated with radiation or surgery who
             are asymptomatic and do not require steroid treatment for at least 4 weeks before
             starting study treatment are eligible; neurosurgical resection of brain metastases or
             brain biopsy is permitted if completed at least 3 months before starting study
             treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or
             magnetic resonance imaging (MRI) scans for participants with known brain metastases is
             required to confirm eligibility

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to erlotinib

          -  The participant has prothrombin time (PT)/international normalized ratio (INR) or
             partial thromboplastin time (PTT) test >= 1.3 the laboratory ULN within 7 days before
             the first dose of study treatment

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Participants with history of chronic diarrhea, grade >= 2 prior to study
             participation; persons with up to grade 1 diarrhea will be eligible

          -  The participant requires chronic concomitant treatment with the following strong
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers OTHER than
             antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin,
             rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing
             anti-convulsant drugs (EIACD), and St. John's Wort; use of efavirenz or etravirine is
             permitted for participants considered for the CYP3A4-inducer based antiretroviral
             therapy (ART) regimen arm (Stratum B) of the trial

               -  Although study participants will be eligible regardless of smoking history,
                  smokers should be strongly advised to stop smoking while on erlotinib; smoking
                  induces cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) enzymes
                  and alters erlotinib exposure by 64%

          -  Participants who take medications that are not recommended for concomitant use with
             their current antiretroviral regimen

          -  The participant requires concomitant treatment with the following inhibitors of
             CYP3A4:

               -  Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin

               -  Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole

               -  Antidepressants: nefazodone

               -  Antidiuretic: conivaptan

               -  Gastrointestinal (GI): cimetidine, aprepitant

               -  Hepatitis C: boceprevir, telaprevir

               -  Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos,
                  star fruit, exotic citrus fruits, or grapefruit hybrids); use of any of
                  anti-retrovirals (delavirdine) or protease inhibitors (ritonavir, indinavir,
                  lopinavir/ritonavir, saquinavir, nelfinavir) is permitted; specifically,
                  ritonavir and cobicistat is permitted for participants considered for the
                  CYP3A4-inhibitor based ART regimen arm (Stratum A) of the trial

          -  Participants should not have significant abnormalities of the cornea based on history
             (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's
             dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein,
             Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar
             tear production test)

          -  Female participants may not be pregnant or breastfeeding; women of childbearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control) prior to study entry and for the duration of study participation;
             should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately

          -  Persons with tumors known to have biomarkers predictive of resistance to erlotinib
             therapy (specifically Kirsten rat sarcoma viral oncogene homolog [KRAS] mutations,
             anaplastic lymphoma receptor tyrosine kinase [ALK] gene rearrangements, and EGFR T790M
             mutations) will be ineligible for study participation; if the results of molecular
             studies are not available or known at the time of study registration and subsequently
             become available, such participants will be considered eligible and if deriving
             clinical benefit may continue receiving erlotinib at the discretion of the
             investigator and study chair