Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments trastuzumab emtansine, trastuzumab, pertuzumab, paclitaxel, epirubicin, doxorubicin, docetaxel, cyclophosphamide, 5-fluorouracil
Phase phase 3
Target HER2
Sponsor Hoffmann-La Roche
Start date January 2014
End date January 2024
Trial size 1846 participants
Trial identifier NCT01966471, 2012-004902-82, BO28407

Summary

This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of trastuzumab emtansine in combination with pertuzumab versus trastuzumab in combination with pertuzumab and a taxane as adjuvant therapy in participants with human epidermal growth (HER) factor 2 (HER2)-positive primary invasive breast cancer. Following surgery and anthracycline-based chemotherapy, participants will receive either trastuzumab emtansine at a dose of 3.6 milligrams per kilogram (mg/kg) and pertuzumab at a dose of 420 milligrams (mg) intravenously (IV) every 3 weeks (q3w) or trastuzumab at a dose of 6 mg/kg and pertuzumab at a dose of 420 mg IV q3w in combination with a taxane.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Primary purpose treatment
Masking no masking
Arm
(Active Comparator)
Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
trastuzumab Herceptin
Trastuzumab IV infusion (duration 90 minutes) will be administered at 8 mg/kg loading dose followed by 6 mg/kg IV q3w for up to 18 cycles (1 cycle = 21 days).
pertuzumab Perjeta
Pertuzumab infusion (duration 60 minutes) will be administered at 840 mg loading dose followed by 420 mg IV q3w for up to 18 cycles (1 cycle = 21 days).
paclitaxel
IV infusion of paclitaxel 80 mg/m^2 once weekly may be administered concurrently with trastuzumab in combination with pertuzumab for 12 weeks.
epirubicin
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using epirubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
doxorubicin
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using doxorubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
docetaxel
IV infusion either docetaxel every 3 weeks (q3w) (at 100 milligram per square meter [mg/m^2] for 3 cycles (1 cycle = 21 days); at 75 mg/m2 for 4 cycles; or start at 75 mg/m^2 in the first cycle and escalate to 100 mg/m^2 if no dose limiting toxicity occurs, for a total of 3 cycles at minimum) may be administered concurrently with trastuzumab in combination with pertuzumab.
cyclophosphamide
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using cyclophosphamide (FEC) may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
5-fluorouracil
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using 5-fluorouracil, may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
(Experimental)
Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
trastuzumab emtansine Kadcyla
Trastuzumab emtansine IV infusion (duration 90 minutes) will be administered at 3.6 mg/kg q3w for up to 18 cycles (1 cycle = 21 days).
epirubicin
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using epirubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
doxorubicin
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using doxorubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
cyclophosphamide
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using cyclophosphamide (FEC) may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
5-fluorouracil
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using 5-fluorouracil, may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.

Primary Outcomes

Measure
Invasive Disease-Free Survival (IDFS) in the Overall Population
time frame: Baseline up to approximately 10 years
IDFS in the Node-Positive Subpopulation
time frame: Baseline up to approximately 10 years

Secondary Outcomes

Measure
IDFS Plus Second Primary Non-Breast Cancer
time frame: Baseline up to approximately 10 years
Disease-Free Survival (DFS)
time frame: Baseline up to approximately 10 years
Distant Recurrence-Free Interval (DRFI)
time frame: Baseline up to approximately 10 years
Overall Survival (OS)
time frame: Baseline up to approximately 10 years
Percentage of Participants With Adverse Events
time frame: Baseline up to approximately 10 years
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
time frame: Baseline up to approximately 10 years
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
time frame: From randomization to 24 months after end of treatment visit (up to approximately 3 years)
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score
time frame: From randomization to 24 months after end of treatment visit (up to approximately 3 years)
Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment
time frame: From randomization to 24 months after end of treatment visit (up to approximately 3 years)

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (/=] 1), any tumor size except T0, and any hormonal receptor status; or Node-negative disease (pN0) with pathologic tumor size >2.0 centimeters by standard local assessment and negative for estrogen receptor (ER) and progesterone receptor (PR) determined by a central pathology laboratory - Participants with synchronous bilateral invasive disease are eligible only if both lesions are HER2-positive - No more than 9 weeks (63 days) may elapse between definitive breast surgery (or the last surgery if additional resection required for breast cancer) and randomization - Baseline left ventricular ejection fraction (LVEF) >/=55% measured by echocardiogram (ECHO; preferred) or multiple-gated acquisition (MUGA) scans - Documentation on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology is required - Female participants of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception. For male participants with partners of childbearing potential, one highly effective form of contraception or two effective forms of contraception must be used. Contraception must continue for the duration of study treatment and for 6 months after the last dose of study treatment Exclusion Criteria: - History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma - History of non-breast malignancies within the 5 years prior to randomization, except for carcinoma in situ (CIS) of the cervix, CIS of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin - Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer - For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (for example, neoadjuvant or adjuvant), including but not limited to, chemotherapy, anti-HER2 therapy (for example, trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intra-operative radiotherapy as a boost at the time of primary surgery is acceptable) - Previous therapy with anthracyclines, taxanes, or HER2-targeted therapy for any malignancy - History of DCIS and/or lobular CIS (LCIS) that was treated with any form of systemic chemotherapy, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed. Participants who had their DCIS/LCIS treated with surgery only and/or contralateral DCIS treated with radiation are allowed to enter the study - Participants with contraindication to RT while adjuvant RT is clinically indicated - Concurrent anti-cancer treatment in another investigational trial - Cardiopulmonary dysfunction as defined by protocol: angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease, significant symptoms (Grade >/=2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia, myocardial infarction within 12 months prior to randomization, uncontrolled hypertension, evidence of transmural infarction on electrocardiogram (ECG), requirement for oxygen therapy - Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes, or known infection with HIV - Any known active liver disease. For participants who are known carriers of HBV/HCV, active hepatitis B/C infection must be ruled out per local guidelines - Inadequate hematologic, renal or liver function - Pregnant or lactating women - Hypersensitivity to any of the study medications or any of the ingredients or excipients of these medications, including hypersensitivity to benzyl alcohol - Chronic immunosuppressive therapies, including systemic corticosteroids

Additional Information

Official title A Randomized, Multicenter, Open-Label, Phase III Trial Comparing Trastuzumab Plus Pertuzumab Plus a Taxane Following Anthracyclines Versus Trastuzumab Emtansine Plus Pertuzumab Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.