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

NCT02144012 | Terminated Phase 3 Results

• 1 other identifier: YO28405
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 8

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (7)

• 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.

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

• 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.

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

• 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.

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

• Percentage of Participants With Adverse Events Leading to Treatment Discontinuation

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

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

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

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

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

• 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.

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

Secondary Outcomes (9)

• Overall Survival (OS)

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

• One-Year Survival Rate

  At 12 months

• OS Truncated at 2 Years

  At 24 months

• Objective Response Rate (ORR)

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

• Duration of Response (DOR)

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

Study Arms (2)

Arm A: Trastuzumab emtansine

EXPERIMENTAL

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.

Drug: Trastuzumab Emtansine

Arm B: Trastuzumab + Docetaxel

ACTIVE COMPARATOR

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.

Drug: Trastuzumab; Drug: Docetaxel

Interventions

Trastuzumab DRUG

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.

Also known as: Herceptin

Arm B: Trastuzumab + Docetaxel

Trastuzumab Emtansine DRUG

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

Also known as: Kadcyla

Arm A: Trastuzumab emtansine

Docetaxel DRUG

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

Arm B: Trastuzumab + Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Unknown Facility

Sabah, Sabah, 88996, Malaysia

Location

Unknown Facility

Daegu, 702-210, South Korea

Location

Unknown Facility

Gyeonggi-do, 410-769, South Korea

Location

Unknown Facility

Seoul, 05505, South Korea

Location

Unknown Facility

Taipei, 00112, Taiwan

Location

Unknown Facility

Taipei, 100, Taiwan

Location

Unknown Facility

Taoyuan District, 333, Taiwan

Location

Unknown Facility

Bangkok, 10330, Thailand

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Ado-Trastuzumab Emtansine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

Due to early termination of the study only limited data from a small subset (49) of the originally planned study population size (561) are available and were too limited to perform originally planned efficacy analyses as specified in the protocol.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: May 21, 2014
• Study Start: June 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: March 7, 2017
• Results First Posted: March 7, 2017

Record last verified: 2017-01

Locations

TH (1); TW (3); KR (3); MY (1)