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A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

NCT02289833

Description:

This is a Phase 2, multicenter study designed to evaluate the efficacy and safety of trastuzumab emtansine administered as a single-agent in participants with HER2-positive (HER2 IHC 2+ or HER2 IHC 3+) advanced or metastatic NSCLC. Participants will be treated with trastuzumab emtansine administered intravenously at a dose of 3.6 milligrams per kilogram (mg/kg) on Day 1 of 21-day cycles until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor, whichever occurs first.

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

Completed

Phase:

Phase 2

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Trastuzumab Emtansine</span> in Patients With <span class="go-doc-concept go-doc-biomarker">HER2</span> <span class="go-doc-concept go-doc-keyword">IHC</span>-Positive, Locally Advanced or Metastatic Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: A Study of Trastuzumab Emtansine in Patients With HER2 IHC-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
  • Official Title: A PHASE 2, MULTICENTER, SINGLE-ARM STUDY OF TRASTUZUMAB EMTANSINE IN PATIENTS WITH HER2 IHC-POSITIVE, LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER WHO HAVE RECEIVED AT LEAST ONE PRIOR CHEMOTHERAPY REGIMEN
  • Clinical Trial IDs

    NCT ID: NCT02289833

    ORG ID: BO29389

    NCI ID: 2014-001237-83

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    trastuzumab emtansine T-DM1; ado-trastuzumab emtansine trastuzumab emtansine

    Trial Purpose

    This is a Phase 2, multicenter, single-arm, two cohort study designed to evaluate the
    efficacy and safety of trastuzumab emtansine as single-agent in patients with HER2-positive
    locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients will be enrolled
    into two separate cohorts, depending on HER2 status: HER2 immunohistochemistry (IHC) 2+ or
    HER2 IHC 3+. Patients in both cohorts will be treated with an intravenous dose of 3.6 mg/kg
    trastuzumab emtansine on Day 1 of 21-day cycles. Patients will remain on study until disease
    progression (as assessed by the investigator), unmanageable toxicity, or study termination
    by the Sponsor.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    trastuzumab emtansine Experimental trastuzumab emtansine

    Eligibility Criteria

    Inclusion Criteria:

    - Age >/= 18 years

    - Histologically or cytologically documented diagnosis of Stage IIIB not amenable to
    radical treatment or Stage IV NSCLC; pathological characterization must determine the
    non-squamous or squamous histological subtype as well as adenocarcinoma subtype
    classification.

    - HER2 status of IHC 2+ or 3+ as determined by a Sponsor-designated central laboratory

    - Prior treatment with at least one regimen of platinum-based (cisplatin or
    carboplatin) chemotherapy in the locally advanced or metastatic setting/recurrent
    NSCLC with documented disease progression by investigator assessment

    - Patients with a known ALK fusion oncogene (must be documented in the patient's chart)
    must have also experienced disease progression or intolerance with a first-line ALK
    Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene
    NSCLC (e.g., crizotinib). Disease progression or intolerance must be documented

    - Patients with a known mutation in the EGFR gene (must be documented in the patient's
    chart) must have also experienced disease progression or intolerance with an EGFR TKI
    approved for the treatment of EGFR-mutant NSCLC (e.g., gefitinib, erlotinib,
    afatinib). Disease progression or intolerance must be documented

    - Measurable disease determined as per the Response Evaluation Criteria in Solid Tumors
    (RECIST), version 1.1

    - Life expectancy >/= 12 weeks

    - Adequate organ function

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Left ventricular ejection fraction (LVEF) >/= 50% by either echocardiogram (ECHO) or
    multiple-gated acquisition (MUGA)

    - Use of highly effective contraception

    Exclusion Criteria:

    Cancer-Related Criteria

    - Any approved anti-cancer therapy </= 21 days (including chemotherapy or hormonal
    therapy) before the first study treatment; the following exceptions are allowed: (1)
    TKIs approved for the treatment of NSCLC must be discontinued > 7 days prior to the
    first study treatment on Cycle 1, Day 1 (The baseline computed tomography scan must
    be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral
    contraceptives; (3) Anti-emetics, GCS-F, prophylactic antibiotics are allowed
    according to local standards

    - Investigational therapy participation in another clinical study with therapeutic
    intent </= 21 days before first study treatment

    - Previous irradiation is permitted if >/= 14 days since the last fraction of
    radiotherapy have elapsed before the first study treatment on Day 1 of Cycle 1 as
    long as a sufficient number of target lesions remain to allow for measurable disease
    as per RECIST v1.1.

    - Patients who have untreated brain metastases or are symptomatic; patients with
    treated brain metastases must have discontinued corticosteroid therapy and not have
    any neurological symptoms

    - History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity
    to trastuzumab or murine proteins or any excipient of the product

    - History of exposure to the following cumulative doses of anthracyclines: Doxorubicin
    or liposomal doxorubicin > 500 mg/m2; Epirubicin > 900 mg/m2; Mitoxantrone > 120
    mg/m2. If another anthracycline, or more than one anthracycline, has been used, the
    cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.

    - Current peripheral neuropathy of Grade >/= 3 per the National Cancer Institute Common
    Toxicity Criteria for Adverse Events (NCI CTCAE) v. 4.0

    - History of other malignancy within the last 5 years, except for appropriately treated
    carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
    or other cancers with a similar outcome as those mentioned above.

    Cardiopulmonary Function Criteria

    - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
    drainage procedures

    - Severe dyspnea at rest due to complications of advanced malignancy or requiring
    current continuous oxygen therapy

    - Clinical history of active hemoptysis

    - Evidence of active pneumonitis during screening

    - Current unstable ventricular arrhythmia requiring treatment

    - History of symptomatic congestive heart failure (CHF; New York Heart Association
    [NYHA] Classes II-IV)

    - History of myocardial infarction or unstable angina within 6 months of enrollment

    - History of a decrease in LVEF to < 50%

    General Criteria

    - Current severe, uncontrolled systemic disease (e.g., clinically significant
    cardiovascular, pulmonary, or metabolic disease)

    - Major surgical procedure or significant traumatic injury within 28 days before
    enrollment or anticipation of the need for major surgery during the course of study
    treatment

    - Current pregnancy or lactation

    - Current known active infection with HIV, hepatitis B, or hepatitis C virus

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective response rate, defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments >/= 4 weeks apart and based on investigator assessment according to RECIST v. 1.1

    Secondary Outcome Measures

    Overall survival (OS)

    Progression-free survival (PFS), defined as the time from first study drug administration to first documented disease progression, by investigator assessment using RECIST v1.1

    Duration of response (DOR), defined as the time from the initial documentation of objective response (CR or PR) to documented disease progression, using RECIST v1.1, or death from any cause

    Serum concentrations of trastuzumab emtansine and total trastuzumab

    Plasma concentration of DM1

    Incidence of adverse events (AEs)

    Trial Keywords