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)

NCT ID: NCT02289833

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-15
• Study Completion Date: 2018-08-20

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort IHC2+

Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.

Group Type: EXPERIMENTAL

Trastuzumab Emtansine

Intervention Type: DRUG

Trastuzumab emtansine will be administered intravenously (IV) at a dose of 3.6 mg/kg on Day 1 of every 21-day cycle until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the sponsor, whichever occurs first.

Cohort IHC3+

Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.

Group Type: EXPERIMENTAL

Trastuzumab Emtansine

Intervention Type: DRUG

Trastuzumab emtansine will be administered intravenously (IV) at a dose of 3.6 mg/kg on Day 1 of every 21-day cycle until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the sponsor, whichever occurs first.

Interventions

Trastuzumab Emtansine

Trastuzumab emtansine will be administered intravenously (IV) at a dose of 3.6 mg/kg on Day 1 of every 21-day cycle until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the sponsor, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

Kadcyla, T-DM1

Eligibility Criteria

Inclusion Criteria

• 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
• Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene (must be documented in the participant'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 (for example, crizotinib). Disease progression or intolerance must be documented
• Participants with a known mutation in the epidermal growth factor receptor (EGFR) gene (must be documented in the participant's chart) must have also experienced disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC (for example, gefitinib, erlotinib, afatinib). Disease progression or intolerance must be documented
• Measurable disease determined as per the RECIST v1.1
• Life expectancy of at least (>/=) 12 weeks
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Left ventricular ejection fraction (LVEF) >/= 50 percent (%) by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
• Use of highly effective contraception

Exclusion Criteria

Cancer-Related Criteria:

• Any approved anti-cancer therapy less than or equal to (</=) 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 greater than (>) 7 days prior to the first study treatment on D1C1 (The baseline computed tomography [CT] scan must be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral contraceptives; (3) Anti-emetics, Granulocyte-colony stimulating factor (GCS-F), and prophylactic antibiotics 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 as long as a sufficient number of target lesions remain to allow for measurable disease as per RECIST v1.1
• Participants who have untreated brain metastases or are symptomatic; participants 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 milligram per meter-square (mg/m^2); Epirubicin > 900 mg/m^2; Mitoxantrone > 120 mg/m^2. If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m^2 doxorubicin
• Peripheral neuropathy of Grade >/= 3 per the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (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 (for example, 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie

Berlin, , Germany

Kaiserswerther Diakonie Florence Nightingale-Krankenh. Tagesklinik f.Onkologie

Düsseldorf, , Germany

Asklepios-Fachkliniken Muenchen-Gauting; Onkologie

Gauting, , Germany

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II

Halle, , Germany

Fachklinik für Lungenerkrankungen

Immenhausen, , Germany

Azienda Ospedaliera Univ Parma; Dept Oncologia Medica

Parma, Emilia-Romagna, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Medical University of Gdansk

Gdansk, , Poland

Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii

Otwock, , Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, , Poland

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center - Oncology

Seoul, , South Korea

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, , Spain

Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia

Zaragoza, , Spain

CHUV; Departement d'Oncologie

Lausanne, , Switzerland

UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie

Zurich, , Switzerland

Countries

United States; Germany; Italy; Poland; South Korea; Spain; Switzerland

Other Identifiers

2014-001237-83

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO29389

Identifier Type: -

Identifier Source: org_study_id