This trial is active, not recruiting.

Condition breast cancer
Treatments anthracycline-based chemotherapy, pertuzumab, taxane, trastuzumab, trastuzumab emtansine
Phase phase 3
Target HER2
Sponsor Hoffmann-La Roche
Start date January 2014
End date February 2018
Trial size 1846 participants
Trial identifier NCT01966471, 2012-004902-82, BO28407


This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of Kadcyla (trastuzumab emtansine, also known as T-DM1) in combination with Perjeta (pertuzumab) versus Herceptin (trastuzumab) in combination with Perjeta and a taxane as adjuvant therapy in patients with HER2-positive primary invasive breast cancer. Following surgery and anthracycline-based chemotherapy, patients will receive either Kadcyla 3.6 mg/kg and Perjeta 420 mg intravenously (iv) every three weeks or Herceptin 6 mg/kg iv every three weeks in combination with Perjeta and a taxane. Anticipated time on HER2 targeted study treatment is up to 1 year. Enrollment is complete for this study and a total of 1846 patients have been randomized.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
(Active Comparator)
anthracycline-based chemotherapy
3 to 4 cycles of standard of care anthracycline-based chemotherapy
pertuzumab Perjeta
840 mg loading dose followed by 420 mg IV q3w
paclitaxel 80 mg/m2 IV qw or docetacel q3w
trastuzumab Herceptin
8 mg/kg loading dose followed by 6 mg/kg IV q3w
anthracycline-based chemotherapy
3 to 4 cycles of standard of care anthracycline-based chemotherapy
pertuzumab Perjeta
840 mg loading dose followed by 420 mg IV q3w
trastuzumab emtansine Kadcyla
3.6 mg/kg IV q3w

Primary Outcomes

Invasive disease-free survival (IDFS), defined as time from randomization to occurrence of ipsilateral breast cancer recurrence, second primary invasive breast cancer, distant recurrence, or death of any cause
time frame: up to approximately 10 years

Secondary Outcomes

IDFS plus second primary non-breast cancer, excluding non-melanoma skin cancers and carcinoma in situ of any site
time frame: up to approximately 10 years
Disease-free survival (DFS), defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS)
time frame: up to approximately 10 years
Distant recurrence-free interval (DRFI), defined as time between randomization and first occurrence of distant breast cancer recurrence
time frame: up to approximately 10 years
Overall survival
time frame: up to approximately 10 years
Safety: Percentage of participants with adverse events
time frame: up to approximately 10 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

  • Adult patients, >/= 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 1
  • Non-metastatic histologically confirmed primary invasive breast carcinoma that was operable
  • HER2-positive breast cancer
  • Known hormone receptor status of the primary tumor
  • Adequately excised: patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
  • Pathological tumor-node-metastasis staging (Union for International Cancer Control-American Joint Committee on Cancer [UICC/AJCC] 7th edition): Eligible patients must have either: Node-positive disease (pN >/= 1), any tumor size except T0, and any hormonal receptor status, or Node-negative disease (pN0) with pathologic tumor size >2.0 cm by standard local assessment AND negative for ER and PR determined by a central pathology laboratory
  • Patients 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 LVEF >/= 55% measured by echocardiogram (ECHO; preferred) or multiple-gated acquisition (MUGA) scans
  • Documentation on hepatitis B virus (HBV) and hepatitic C virus (HCV) serologies is required
  • Female patients of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal contraception. For male patients 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 (e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy, anti-HER2 therapy (e.g., trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intraoperative 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 LCIS that was treated with any form of systemic chemotherapy, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed. Patients who had their DCIS/LCIS treated with surgery only and/or contralateral DCIS treated with radiation are allowed to enter the study
  • Patients 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 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 patients 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

Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in August 2016.