Clinical Trials /

Erlotinib Hydrochloride in Treating Non-Small Cell Lung Cancer That is Metastatic or Cannot be Removed by Surgery in Patients With HIV Infection

NCT02134886

Description:

This phase I trial studies the side effects and best dose of erlotinib hydrochloride in treating non-small cell lung cancer that has spread to other parts of the body or cannot be removed by surgery in patients with human immunodeficiency virus (HIV) infection. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride is a standard drug used for treating lung cancer, however, it is not yet known whether it is safe to give erlotinib hydrochloride to patients who also have HIV infection or not.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Erlotinib Hydrochloride</span> in Treating Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> That is Metastatic or Cannot be Removed by Surgery in Patients With HIV Infection

Title

  • Brief Title: Erlotinib Hydrochloride in Treating Non-Small Cell Lung Cancer That is Metastatic or Cannot be Removed by Surgery in Patients With HIV Infection
  • Official Title: A Phase I/Pharmacokinetic Study of Erlotinib for Advanced Non-small Cell Lung Cancer in Persons With HIV Infection
  • Clinical Trial IDs

    NCT ID: NCT02134886

    ORG ID: NCI-2014-00684

    NCI ID: NCI-2014-00684

    Trial 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

    Trial Interventions

    Drug Synonyms Arms
    Erlotinib Hydrochloride Cp-358,774, ERLOTINIB HYDROCHLORIDE, OSI-774, Tarceva Treatment (erlotinib hydrochloride)

    Trial Purpose

    This phase I trial studies the side effects and best dose of erlotinib hydrochloride in
    treating non-small cell lung cancer that has spread to other parts of the body or cannot be
    removed by surgery in patients with human immunodeficiency virus (HIV) infection. Erlotinib
    hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
    cell growth. Erlotinib hydrochloride is a standard drug used for treating lung cancer,
    however, it is not yet known whether it is safe to give erlotinib hydrochloride to patients
    who also have HIV infection or not.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate the safety and tolerability of erlotinib (erlotinib hydrochloride) as a
    single agent in non-small cell lung cancer participants with HIV infection and to determine
    the maximum tolerated dose of erlotinib in combination with antiretroviral therapy in this
    participant population.

    SECONDARY OBJECTIVES:

    I. To evaluate the efficacy of erlotinib in advanced non-small cell lung cancer persons with
    HIV infection.

    II. To investigate possible pharmacokinetic interactions between erlotinib and
    antiretroviral therapy in persons with HIV infection, while accounting for nicotine
    exposure.

    III. To investigate the effects of therapy on participant immune status and HIV viral load.

    IV. To preliminarily evaluate known molecular and phenotypic correlates of improved clinical
    outcomes associated with epidermal growth factor receptor (EGFR) inhibitors.

    OUTLINE: This is a dose-escalation study.

    Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
    repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up for 30 days.

    Trial Arms

    Name Type Description Interventions
    Treatment (erlotinib hydrochloride) Experimental Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of toxicities evaluated with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0)

    Maximum tolerated dose of erlotinib hydrochloride defined as the dose level in which less than or equal to 1 out of 6 participants experiences dose-limiting toxicity evaluated with NCI CTCAE v4.0

    Secondary Outcome Measures

    CD4+ counts

    CD8+ counts

    HIV viral load

    Incidence of erlotinib hydrochloride-associated skin rash

    Pharmacokinetic parameters of erlotinib hydrochloride, including half-life (T1/2), clearance (Cl), and area under the curve (AUC)

    Response assessed via RECIST 1.1

    Trial Keywords