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

Metastatic Breast Cancer Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02144012
• Other study ID #: YO28405
• Status: Completed
• Phase: Phase 3
• First received: May 19, 2014
• Last updated: November 4, 2016
• Start date: July 2014
• Est. completion date: January 2016

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, randomized, multicenter, multinational, two-arm, open-label clinical trial to investigate a first-line treatment of patients with 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 multimodality therapy, and/or metastatic BC if they have not received prior chemotherapy for their metastatic disease. Eligible patients 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) and will receive 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• trastuzumab + docetaxel
For the first cycle, trastuzumab 8 mg/kg IV plus docetaxel at either 75 mg/m2 or 100 mg/m2 IV. For the subsequent cycles, trastuzumab 6 mg/kg IV plus docetaxel 75 mg/m2 or 100 mg/m2 IV Q3W
• trastuzumab emtansine
trastuzumab emtansine 3.6 mg/kg intravenous (IV) over 30-90 minutes every 3 weeks (Q3W)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Korea, Republic of,  Malaysia,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival, defined as the time from randomization to the first occurrence of disease progression (with the use of RECIST v1.1) or death from any cause, whichever occurs first, on the basis of investigator assessments		Up to 66 months	No
Primary	Safety: Incidence of adverse events (AEs)		Up to 66 months	No
Secondary	Overall survival (OS), defined as the time from the date of randomization to the date of death from any cause		Up to 66 months	No
Secondary	One-year survival rate, Kaplan-Meier estimates		Up to 66 months	No
Secondary	OS truncated at 2 years, 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 patient's randomization date censored at 2 years		Up to 66 months	No
Secondary	Objective response rate (ORR), defined as partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1		Up to 66 months	No
Secondary	Duration of response (DOR), defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study		Up to 66 months	No