Clinical Trials /

Erlotinib Hydrochloride and Onalespib Lactate in Treating Patients With Recurrent or Metastatic EGFR-Mutant Non-small Cell Lung Cancer

NCT02535338

Description:

This phase I/II trial studies the side effects and best dose of onalespib lactate when given together with erlotinib hydrochloride and to see how well they work in treating patients with EGFR-mutant non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Erlotinib hydrochloride and onalespib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Erlotinib Hydrochloride</span> and Hsp90 Inhibitor AT13387 in Treating Patients With Recurrent or Metastatic Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Erlotinib Hydrochloride and Hsp90 Inhibitor AT13387 in Treating Patients With Recurrent or Metastatic Non-small Cell Lung Cancer
  • Official Title: A Phase I/II Trial of Erlotinib and AT13387 (Onalespib Lactate) in EGFR-Mutant Non-small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02535338

    ORG ID: NCI-2015-01411

    NCI ID: NCI-2015-01411

    Trial Conditions

    Recurrent Non-Small Cell Lung Carcinoma

    Stage IV Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Erlotinib Hydrochloride Cp-358,774, OSI-774, Tarceva Treatment (erlotinib hydrochloride, Hsp90 inhibitor AT13387)
    Hsp90 Inhibitor AT13387 AT13387 Treatment (erlotinib hydrochloride, Hsp90 inhibitor AT13387)

    Trial Purpose

    This phase I/II trial studies the side effects and best dose of heat shock protein 90
    (Hsp90) inhibitor AT13387 when given together with erlotinib hydrochloride and to see how
    well they work in treating patients with non-small cell lung cancer that has come back
    (recurrent) or has spread to other places in the body (metastatic). Erlotinib hydrochloride
    and Hsp90 inhibitor AT13387 may stop the growth of tumor cells by blocking some of the
    enzymes needed for cell growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the safety and tolerability of erlotinib (erlotinib hydrochloride) and
    AT13387 (Hsp90 inhibitor AT13387) in patients with epidermal growth factor receptor
    (EGFR)-mutant non-small cell lung cancer (NSCLC). (PHASE I) II. To preliminarily assess
    efficacy of combination erlotinib and AT13387 at the recommended phase II dose (RP2D)
    determined in the phase I portion of the study in EGFR-mutant NSCLC patients who have not
    had a complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST)
    1.1 to frontline erlotinib within 6 months. (PHASE II, COHORT A) III. To preliminarily
    assess efficacy of combination erlotinib and AT13387 at the RP2D in NSCLC patients whose
    tumor harbors an EGFR Exon 20 Insertion (an EGFR mutation not typically responsive to single
    agent erlotinib). (PHASE II, COHORT B)

    SECONDARY OBJECTIVES:

    I. To observe and record anti-tumor activity (primary aim phase II, secondary aim phase I).

    II. To evaluate in a preliminary manner the progression-free survival (PFS) and disease
    control rate (DCR) of patients treated with erlotinib/AT13387.

    III. To characterize the pharmacokinetics of the above drug combinations at the recommended
    phase II dose (RP2D).

    TERTIARY OBJECTIVES:

    I. To explore plasma EGFR-mutant deoxyribonucleic acid (DNA) as a biomarker by detecting
    changes in plasma EGFR-mutant DNA levels (including plasma EGFR-T790M) and new mutations
    that may represent resistance to treatment.

    II. To demonstrate knockdown of Hsp90 client oncoproteins via treatment with erlotinib and
    AT13387 by multiplexed immunofluorescence in serial tumor biopsies.

    III. To establish patient derived xenotransplant models in EGFR-mutated NSCLC with a focus
    on tumors that lack response to single agent erlotinib and in patients with tumors harboring
    EGFR exon 20 insertions.

    OUTLINE: This is a phase I, dose-escalation study of Hsp90 inhibitor AT13387 followed by a
    phase II study.

    Patients receive erlotinib hydrochloride orally (PO) daily and Hsp90 inhibitor AT13387
    intravenously (IV) over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at
    least 3 courses in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 12 weeks for 1 year and
    then annually thereafter.

    Trial Arms

    Name Type Description Interventions
    Treatment (erlotinib hydrochloride, Hsp90 inhibitor AT13387) Experimental Patients receive erlotinib hydrochloride PO daily and Hsp90 inhibitor AT13387 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride, Hsp90 Inhibitor AT13387

    Eligibility Criteria

    Inclusion Criteria:

    - PHASE I: Patients must have metastatic/recurrent, histologically confirmed NSCLC that
    harbors an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X,
    Exon 21 L861Q) with progressive disease by RECIST 1.1 on a previous EGFR-tyrosine
    kinase inhibitor (TKI) or; patients must have metastatic/recurrent histologically
    confirmed NSCLC that harbors an EGFR Exon 20 insertion with progressive disease on
    platinum containing chemotherapy

    - PHASE II COHORT A: Patients must have metastatic/recurrent histologically confirmed
    NSCLC that harbors an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon
    18 G719X, Exon 21 L861Q) with stable disease by RECIST 1.1 as best response on
    erlotinib compared to pre-treatment erlotinib imaging by RECIST 1.1 or progressive
    disease compared to pre-treatment imaging by RECIST 1.1; patients must be enrolled
    within 6 months of initiation of erlotinib

    - PHASE II COHORT B: Patients must have metastatic/recurrent histologically confirmed
    NSCLC that harbors an EGFR Exon 20 insertion with progressive disease on platinum
    doublet chemotherapy

    - FOR PHASE I: if patient is on erlotinib at the time of signed consent, the patient
    does not need to be discontinued prior to initiation of erlotinib and AT13387; other
    EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and
    AT13387

    - FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent,
    erlotinib does not need to be discontinued prior to receiving treatment erlotinib and
    AT13387; last dose of erlotinib must be less than 28 days from when patient signs
    consent

    - FOR PHASE II COHORT B: (EGFR Exon 20 Insertions): Prior EGFR-TKIs including erlotinib
    is allowed; if patient is on erlotinib at the time of signed consent, erlotinib does
    not need to be discontinued prior to initiation of erlotinib and AT13387

    - Local testing for EGFR-mutations for this study is acceptable provided it was
    performed in a Clinical Laboratory Improvement Amendment (CLIA) certified lab

    - Patients with a prior history of brain metastases are eligible provided:

    - The brain metastases have been treated

    - The patient is asymptomatic from the brain metastases

    - Corticosteroids prescribed for the management of brain metastases have been
    discontinued at least 7 days prior to registration

    - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks
    prior to receiving study drugs

    - Patients must have recovered from adverse events attributable to previous treatment
    to =< grade 1, except for alopecia and sensory neuropathy =< grade 2

    - Patients must have the ability to swallow tablets

    - Measurable disease by RECIST 1.1

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

    - Life expectancy of greater than 3 months

    - Leukocytes >= 3,000/mcL

    - Absolute neutrophil count >= 1,500/mcL

    - Platelets >= 100,000/mcL

    - Total bilirubin within normal institutional limits

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

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

    - 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 and/or AT13387
    administration

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

    Exclusion Criteria:

    - Patients who are receiving any other investigational agents

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to erlotinib and/or AT13387

    - History of pneumonitis attributed to an EGFR inhibitor; history of radiation
    pneumonitis is allowed provided steroid administration for pneumonitis was not
    required

    - Strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and
    inhibitors should be avoided; selection of alternate concomitant medications with no
    or minimal CYP3A4 enzyme inhibition potential is recommended; as part of the
    enrollment/informed consent procedures, the patient will be counseled on the risk of
    interactions with other agents, and what to do if new medications need to be
    prescribed or if the patient is considering a new over-the-counter medicine or herbal
    product

    - 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

    - Pregnant women are excluded from this study; breastfeeding should be discontinued if
    the mother is treated with erlotinib and AT13387

    - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
    therapy are ineligible

    - Prior treatment with a Hsp90 inhibitor

    - Treatment with proton pump inhibitors within 3 days prior to study entry; H2-blockers
    are allowed by should be spaced 12 hours apart from erlotinib administration

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of dose-limiting toxicities (DLT) from Hsp90 inhibitor AT13387 in combination with erlotinib hydrochloride graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)

    Tumor response by RECIST criteria (Phase II)

    Secondary Outcome Measures

    Progression-free survival (PFS)

    Tumor response by RECIST criteria (Phase I)

    Trial Keywords