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A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer

Primary Purpose

Metastatic Breast Cancer

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Trastuzumab

Trastuzumab Emtansine

Docetaxel

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age >/= 18 years
HER2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or in situ hybridization positivity, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment
Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease appropriate for chemotherapy
Patients must have measurable and/or non-measurable disease that is evaluable per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Adequate organ function
For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use two adequate non-hormonal forms of contraception during treatment and for at least 6 months after the last dose of study drug

Exclusion Criteria:

Pregnancy or lactation
Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures, except bone fractures because of disease under study)
Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
Current peripheral neuropathy Grade >/= 2 per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0)
History of systemic anti-cancer therapy after the diagnosis of metastatic breast cancer (MBC) or for recurrent locally advanced disease, with the exception of prior hormonal regimens for recurrent locally advanced disease or MBC
An interval of < 12 months after the last dose of vinca alkaloid or taxane chemotherapy (i.e., for treatment of early stage, non-metastatic disease)
Hormonal therapy < 7 days prior to randomization
Trastuzumab < 21 days prior to randomization
Lapatinib </= 14 days prior to randomization
Prior trastuzumab emtansine therapy
Treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization
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 malignancies with an expected curative outcome
Current chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisone equivalent)
History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, docetaxel or paclitaxel
Known hypersensitivity any of the study drugs, including excipients, or any drugs formulated in polysorbate 80

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A: Trastuzumab emtansine

Arm B: Trastuzumab + Docetaxel

Arm Description

Participants will be administered trastuzumab emtansine once every three weeks (Q3W). Participants may remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.

Participants will be administered trastuzumab plus docetaxel Q3W. Participants may remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)

PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.

Safety: Percentage of Participants With Adverse Events (AEs)

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Safety: Percentage of Participants With Grade 3 and 4 AEs

Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 was defined as life-threatening consequences; urgent intervention indicated.

Percentage of Participants With Adverse Events Leading to Treatment Discontinuation

Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption

Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction

Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)

Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF.

Secondary Outcome Measures

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death from any cause.

One-Year Survival Rate

One-year survival rate as determined by Kaplan-Meier estimates.

OS Truncated at 2 Years

OS truncated at 2 years was defined as the time from the date of randomization to the date of death from any cause, with deaths occurring beyond 2 years after the participant's randomization date censored at 2 years.

Objective Response Rate (ORR)

ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1. Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR.

Duration of Response (DOR)

DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study. CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions. Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions.

Pharmacokinetics: Serum Concentrations of Study Medications

Pharmacokinetic (PK) parameters were to be determined in a subset of participants. PK samples from the first 100 Chinese participants were planned to be collected.

Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine

Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire

The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer.

Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire

The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy. The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective.

Full Information

NCT ID

NCT02144012

First Posted

May 19, 2014

Last Updated

January 18, 2017

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02144012

Brief Title

A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer

Official Title

A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel as First-Line Treatment of Patients With Her2-Positive Progressive Or Recurrent Locally Advanced Or Metastatic Breast Cancer.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Terminated

Study Start Date

June 2014 (undefined)

Primary Completion Date

January 2016 (Actual)

Study Completion Date

January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

This is a Phase III, randomized, multicenter, multinational, two-arm, open-label clinical trial to investigate a first-line treatment of participants with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer. The study will enroll patients with HER2-positive, unresectable, locally advanced breast cancer (BC) if they have recurrent disease or progressive disease (PD) despite primary multi-modality therapy, and/or metastatic BC if they have not received prior chemotherapy for their metastatic disease. Eligible participants at up to approximately 40 sites in the Asia-Pacific region will be randomized in a 2:1 ratio to receive trastuzumab emtansine (Arm A) or trastuzumab plus docetaxel (Arm B). All study drugs will be administered at in-clinic visits occurring every three weeks during the treatment phase. Trastuzumab plus docetaxel was chosen as the comparator in the control group (Arm B), as it represents a common first-line treatment option used in this patient population in China and other Asia-Pacific countries.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Trastuzumab emtansine

Arm Type

Experimental

Arm Description

Arm Title

Arm B: Trastuzumab + Docetaxel

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

Herceptin

Intervention Description

For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W.

Intervention Type

Drug

Intervention Name(s)

Trastuzumab Emtansine

Other Intervention Name(s)

Kadcyla

Intervention Description

Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Docetaxel was administered IV at either 75 milligrams/square meter (mg/m^2) or 100 mg/m^2 Q3W.

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Safety: Percentage of Participants With Adverse Events (AEs)

Description

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Safety: Percentage of Participants With Grade 3 and 4 AEs

Description

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Percentage of Participants With Adverse Events Leading to Treatment Discontinuation

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)

Description

Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF.

Time Frame

At time of clinical data cut-off (up to 20 months)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

OS was defined as the time from the date of randomization to the date of death from any cause.

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

One-Year Survival Rate

Description

One-year survival rate as determined by Kaplan-Meier estimates.

Time Frame

At 12 months

Title

OS Truncated at 2 Years

Description

Time Frame

At 24 months

Title

Objective Response Rate (ORR)

Description

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Duration of Response (DOR)

Description

Time Frame

At time of clinical data cut-off (up to 20 months)

Title

Pharmacokinetics: Serum Concentrations of Study Medications

Description

Pharmacokinetic (PK) parameters were to be determined in a subset of participants. PK samples from the first 100 Chinese participants were planned to be collected.

Time Frame

Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)

Title

Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine

Time Frame

Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)

Title

Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire

Description

Time Frame

On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)

Title

Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire

Description

Time Frame

Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >/= 18 years HER2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or in situ hybridization positivity, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease appropriate for chemotherapy Patients must have measurable and/or non-measurable disease that is evaluable per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Adequate organ function For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use two adequate non-hormonal forms of contraception during treatment and for at least 6 months after the last dose of study drug Exclusion Criteria: Pregnancy or lactation Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures, except bone fractures because of disease under study) Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment Current peripheral neuropathy Grade >/= 2 per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0) History of systemic anti-cancer therapy after the diagnosis of metastatic breast cancer (MBC) or for recurrent locally advanced disease, with the exception of prior hormonal regimens for recurrent locally advanced disease or MBC An interval of < 12 months after the last dose of vinca alkaloid or taxane chemotherapy (i.e., for treatment of early stage, non-metastatic disease) Hormonal therapy < 7 days prior to randomization Trastuzumab < 21 days prior to randomization Lapatinib </= 14 days prior to randomization Prior trastuzumab emtansine therapy Treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization 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 malignancies with an expected curative outcome Current chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisone equivalent) History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, docetaxel or paclitaxel Known hypersensitivity any of the study drugs, including excipients, or any drugs formulated in polysorbate 80

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

City

Daegu

ZIP/Postal Code

702-210

Country

Korea, Republic of

City

Gyeonggi-do

ZIP/Postal Code

410-769

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

City

Sabah

ZIP/Postal Code

88996

Country

Malaysia

City

Taipei

ZIP/Postal Code

00112

Country

Taiwan

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

City

Taoyuan

ZIP/Postal Code

333

Country

Taiwan

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

12. IPD Sharing Statement

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer

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