Description:
This two-cohort, open-label, multicenter study will assess the safety, efficacy and
tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced
breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and
chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general
participant population; Cohort 2 will include only Asian participants.
Title
- Brief Title: A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer Who Have Received Prior Anti-HER2 And Chemotherapy-based Treatment
- Official Title: A Two-Cohort, Open-Label, Multicenter Study of Trastuzumab Emtansine (T-DM1) in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment
Clinical Trial IDs
- ORG STUDY ID:
MO28231
- SECONDARY ID:
2012-001628-37
- NCT ID:
NCT01702571
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Trastuzumab Emtansine | RO5304020, T-DM1, Kadcyla | Trastuzumab Emtansine (All Participants) |
Purpose
This two-cohort, open-label, multicenter study will assess the safety, efficacy and
tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced
breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and
chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general
participant population; Cohort 2 will include only Asian participants.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Trastuzumab Emtansine (All Participants) | Experimental | This cohort will enroll all participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression. | |
| Trastuzumab Emtansine (Asian Participants) | Experimental | This cohort will enroll Asian race participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression. | |
Eligibility Criteria
Inclusion Criteria:
- HER2-positive disease determined locally
- Histologically or cytologically confirmed invasive breast cancer
- Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or
metastatic setting must include both chemotherapy, alone or in combination with
another agent, and an anti-HER2 agent, alone or in combination with another agent
- Documented progression of incurable, unresectable, LABC, or mBC, defined by the
investigator: progression must occur during or after most recent treatment for
LABC/mBC or within 6 months of completing adjuvant therapy
- Measurable and/or non-measurable disease
- Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or
multiple-gated acquisition scan (MUGA)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
- Adequate organ function
- Use of highly effective contraception as defined by the protocol
Exclusion Criteria:
- History of treatment with trastuzumab emtansine
- Prior enrollment into a clinical study containing trastuzumab emtansine regardless of
having received trastuzumab emtansine or not
- Peripheral neuropathy of Grade >/= 3 per National Cancer Institute (NCI) common
terminology criteria for adverse events (CTCAE) v 4.0
- History of other malignancy within the previous 5 years, except for appropriately
treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine
cancer, synchronous or previously diagnosed HER2-positive breast cancer
- History of receiving any anti-cancer drug/biologic or investigational treatment within
21 days prior to first study treatment except hormone therapy, which can be given up
to 7 days prior to first study treatment; recovery of treatment-related toxicity
consistent with other eligibility criteria
- History of exposure to cumulative doses of anthracyclines
- History of radiation therapy within 14 days of first study treatment. The participant
must have recovered from any resulting acute toxicity (to Grade </=1) prior to first
study treatment.
- Metastatic central nervous system (CNS) disease only
- Brain metastases which are symptomatic
- History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart
failure (CHF) with previous trastuzumab treatment
- History of symptomatic CHF (New York Heart Association [NYHA] Classes II-IV) or
serious cardiac arrhythmia requiring treatment
- History of myocardial infarction or unstable angina within 6 months of first study
treatment
- Current dyspnea at rest due to complications of advanced malignancy or requirement for
continuous oxygen therapy
- Current severe, uncontrolled systemic disease (clinically significant cardiovascular,
pulmonary, or metabolic disease)
- Pregnancy or lactation
- Currently known active infection with human immunodeficiency virus (HIV), hepatitis B
virus, or hepatitis C virus
- History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to
trastuzumab or murine proteins or any component of the product
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants With Adverse Events of Primary Interest (AEPIs) |
| Time Frame: | Baseline up to approximately 7 years |
| Safety Issue: | |
| Description: | The AEPIs in this study were defined as the following: adverse events (AEs) Grade >/= 3, specifically, hepatic events, allergic reactions, thrombocytopenia and hemorrhage events, all Grade >/= 3 AEs related to trastuzumab emtansine and pneumonitis events of all grades. |
Secondary Outcome Measures
| Measure: | Percentage of Participants With Specific AEPIs |
| Time Frame: | Baseline up to approximately 7 years |
| Safety Issue: | |
| Description: | The AEPIs in this study were defined as the following: adverse events (AEs) Grade >/= 3, specifically, hepatic events, allergic reactions, thrombocytopenia and hemorrhage events, all Grade >/= 3 AEs related to trastuzumab emtansine and pneumonitis events of all grades. |
| Measure: | Percentage of Participants With Adverse Events of Special Interest (AESIs) |
| Time Frame: | Baseline up to approximately 7 years |
| Safety Issue: | |
| Description: | AESIs included: 1) Potential drug-induced liver injury, which included any potential case of drug-induced liver injury as, assessed by laboratory criteria for Hy's law (AST and/or ALT elevations that were >3 × ULN, Concurrent elevation of total bilirubin >2 × ULN (or clinical jaundice if total bilirubin measures were not available), except in participants with documented Gilbert's syndrome. Those with Gilbert's syndrome, elevation of direct bilirubin >2 × ULN was used instead. 2) Suspected transmission of an infectious agent by study drug was defined as any organism, virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform encephalopathy), pathogenic or non-pathogenic. A transmission of an infectious agent suspected from clinical symptoms or laboratory findings indicating an infection in a participant exposed to a medicinal product. |
| Measure: | Progression-Free Survival According to Response Evaluation for Solid Tumors (RECIST) Version (v) 1.1 As Per Investigator Assessment |
| Time Frame: | Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years) |
| Safety Issue: | |
| Description: | Progression free survival is defined as the time (in months) between the date of first dose and the date of disease progression or death from any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm). |
| Measure: | Overall Survival |
| Time Frame: | Baseline until death (up to approximately 7 years) |
| Safety Issue: | |
| Description: | Overall survival is defined as time to death, which is the time from the date of dosing until the date of death, regardless of the cause of death. |
| Measure: | Percentage of Participants With Best Overall Response (Complete Response [CR] or Partial Response [PR]) According to RECIST v 1.1 As Per Investigator Assessment |
| Time Frame: | Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years) |
| Safety Issue: | |
| Description: | Best Overall Response reported here is the Best confirmed Overall Response. To be assigned a status of PR or CR, i.e., to be a responder, changes in tumor measurements had to be confirmed by repeat assessments that had to be performed no less than 4 weeks after the criteria for response were first met, i.e., participants needed to have two consecutive assessments of PR or CR. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. |
| Measure: | Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD]) According to RECIST v 1.1 |
| Time Frame: | Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years) |
| Safety Issue: | |
| Description: | Clinical Benefit was defined as CR plus PR plus SD. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD: neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. |
| Measure: | Duration of Response (DOR) According to RECIST v 1.1 |
| Time Frame: | Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years) |
| Safety Issue: | |
| Description: | DOR is defined as the period from the date of initial confirmed PR or CR (whichever occurs first) until the date of PD or death from any cause. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm). |
| Measure: | Time to Response According to RECIST v 1.1 |
| Time Frame: | Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years) |
| Safety Issue: | |
| Description: | Time to Response is defined as the time from first dose to first documentation of confirmed PR or CR (whichever occurs first). CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. |
| Measure: | Number of Hospital Visits |
| Time Frame: | Baseline up to approximately 7 years |
| Safety Issue: | |
| Description: | The number of hospital visits were recorded to evaluate the resoruce expenditures while participants were on study treatment. |
| Measure: | Type of Hospital Visits |
| Time Frame: | Baseline up to approximately 7 years |
| Safety Issue: | |
| Description: | The type of hospital visits (intensive care unit (ICU) versus other) were recorded to evaluate the resoruce expenditures while participants were on study treatment. The number of participants with at least one ICU visit are based on the number of participants with at least one hospital visit, in each group. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 5, 2021
