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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02144012
• Date of registration: 19/05/2014
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public 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
• Scientific 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.
• Date of first enrolment: June 2014
• Target sample size: 49
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02144012
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

China, Korea, Republic of, Malaysia, Philippines, Taiwan, Thailand

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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
- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Breast Cancer

Intervention(s)

Drug: Docetaxel

Drug: Trastuzumab

Drug: Trastuzumab Emtansine

Primary Outcome(s)

Safety: Percentage of Participants With Adverse Events (AEs) [Time Frame: At time of clinical data cut-off (up to 20 months)]

Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption [Time Frame: At time of clinical data cut-off (up to 20 months)]

Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF) [Time Frame: At time of clinical data cut-off (up to 20 months)]

Safety: Percentage of Participants With Grade 3 and 4 AEs [Time Frame: At time of clinical data cut-off (up to 20 months)]

Percentage of Participants With Adverse Events Leading to Treatment Discontinuation [Time Frame: At time of clinical data cut-off (up to 20 months)]

Progression-Free Survival (PFS) [Time Frame: At time of clinical data cut-off (up to 20 months)]

Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction [Time Frame: At time of clinical data cut-off (up to 20 months)]

Secondary Outcome(s)

One-Year Survival Rate [Time Frame: At 12 months]

OS Truncated at 2 Years [Time Frame: At 24 months]

Duration of Response (DOR) [Time Frame: At time of clinical data cut-off (up to 20 months)]

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

Objective Response Rate (ORR) [Time Frame: At time of clinical data cut-off (up to 20 months)]

Overall Survival (OS) [Time Frame: At time of clinical data cut-off (up to 20 months)]

Pharmacokinetics: Serum Concentrations of Study Medications [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)]

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

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)]

Secondary ID(s)

YO28405

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 07/03/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02144012