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Non-Small Cell Lung CancerPhase 2NCT02289833

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)

A Phase 2 study testing Trastuzumab Emtansine in people with Non-Small Cell Lung Cancer, run by Hoffmann-La Roche at 23 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Trastuzumab Emtansine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
23 sitesin 7 countries
Study dates
15 Dec 2014to 20 Aug 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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)

Trial locations and contacts

23 sites in 7 countries.

23 sites in 7 countries

United States5 sites

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

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

    Jacksonville, Florida, 32256

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

Germany5 sites

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

    Berlin, 14165

  • Kaiserswerther Diakonie Florence Nightingale-Krankenh. Tagesklinik f.Onkologie

    Düsseldorf, 40489

  • Asklepios-Fachkliniken Muenchen-Gauting; Onkologie

    Gauting, 82131

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

    Halle, 06120

  • Fachklinik für Lungenerkrankungen

    Immenhausen, 34376

Other trials in Germany

Spain4 sites

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, 28034

  • Hospital Universitario La Paz; Servicio de Oncologia

    Madrid, 28046

  • Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia

    Zaragoza, 50009

Other trials in Spain

Poland3 sites

  • Medical University of Gdansk

    Gdansk, 80-211

  • Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii

    Otwock, 05-400

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

    Warsaw, 02-781

Other trials in Poland

Italy2 sites

  • Istituto Europeo Di Oncologia

    Milan, Lombardy, 20141

  • Azienda Ospedaliera Univ Parma; Dept Oncologia Medica

    Parma, Emilia-Romagna, 43100

Other trials in Italy

South Korea2 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center - Oncology

    Seoul, 05505

Other trials in South Korea

Switzerland2 sites

  • CHUV; Departement d'Oncologie

    Lausanne, 1011

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

    Zurich, 8091

Other trials in Switzerland

About this study

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

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.

Being tested
Trastuzumab Emtansine
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab EmtansineDrug

    Also called Kadcyla, T-DM1

    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.

Study groups in NCT02289833
Study groupRoleWhat they receive
Cohort IHC2+ExperimentalParticipants 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.
Receives: Drug: Trastuzumab Emtansine
Cohort IHC3+ExperimentalParticipants 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.
Receives: Drug: Trastuzumab Emtansine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1)

    Objective response is defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments ≥ 4 weeks apart, based on investigator assessment according to RECIST, Version 1.1. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeters (mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)

Secondary outcomes (15)

  1. Percentage of Participants Who Died

    Measured: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

  2. Overall Survival (OS)

    OS is defined as the time from first study drug administration to death from any cause.

    Measured: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

  3. Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death

    PFS is defined as the time from first study drug administration to first documented disease progression, based on investigator assessment using RECIST, v1.1, or death from any cause during the study, whichever occurs first. Disease progression is defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

    Measured: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

  4. Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1

    PFS is defined as the time from first study drug administration to first documented disease progression, based on investigator assessment using RECIST, v1.1, or death from any cause during the study, whichever occurs first. Disease progression is defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

    Measured: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

  5. Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1

    DOR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

    Measured: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

  6. Duration of Objective Response (DOR) Assessed According to RECIST v1.1

    DoR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

    Measured: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

  7. Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1

    Clinical benefit is defined as having a CR or PR or stable disease (using RECIST, v1.1) at 6 months. Participants with no post-baseline response assessment are considered as experiencing no clinical benefit. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum while in the study. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

    Measured: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

  8. Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, whether or not considered related to the study drug. A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.

    Measured: From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)

  9. Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab

    Cmax is the 0-21 day maximum observed concentration of a drug and was measured in blood serum.

    Measured: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycles 1 and 3 (one cycle=21 days); at treatment discontinuation/early termination, up to primary analysis, approx. 22 months

  10. AUCinf for Trastuzumab Emtansine and Total Trastuzumab

    AUC (from zero to infinity) represents the total drug exposure over time in blood serum.

    Measured: Pre-dose & 30 minutes (min) post-infusion (inf.) on Day (D) 1 of Cycles (C) 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D1 of C2 & D1 of C 4 (C=21 D); at discontin./termination, up to primary analysis, approx. 22 months

  11. Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab

    t1/2 is the time required for the drug serum concentration to be reduced to half.

    Measured: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin./early termination, up to primary analysis, approx. 22 months

  12. Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab

    Vss is the volume of distribution of study drug at steady state.

    Measured: Pre-dose & 30 minutes (min) post-infusion (inf.) on D1 of C1 & 3; post- inf. on D2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months

  13. Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab

    CL is a measure of the body's elimination of a drug from blood serum over time.

    Measured: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months

  14. Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)

    Cmax is the maximum observed concentration of a drug and was measured in blood plasma.

    Measured: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycle 1 (one cycle=21 days); at treatment discontinuation/early termination,up to primary analysis, approx. 22 months

  15. Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)

    The presence of ADAs in blood serum is an indication of the body's immune response to a drug.

    Measured: Pre-dose (within 2 days) on Day 1 of Cycles 1 and 3; at treatment discontinuation/early termination,up to primary analysis, approx. 22 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2014 (estimated)
  2. Study start15 Dec 2014
  3. Primary completion25 Oct 2016
  4. Study completion20 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02289833
Sponsor's protocol ID
BO29389
Other IDs
2014-001237-83, 2014
Status last verified
Jul 2019
First submitted
4 Nov 2014
Last updated
7 Aug 2019
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab Emtansine in people with Non-Small Cell Lung Cancer, run by Hoffmann-La Roche at 23 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Germany, Spain, Poland, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1) (time frame: From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02289833.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.

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