A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 27 June 2022
• Main ID: NCT01966471
• Date of registration: 17/10/2013
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer
• Scientific 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
• Date of first enrolment: January 31, 2014
• Target sample size: 1846
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01966471
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, Colombia, Czech Republic, Czechia, El Salvador, France, Georgia, Germany, Guatemala, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Norway, Panama, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States, Uruguay

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
(
- 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: participants 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
participants must have either:

Node-positive disease (pN more 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



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

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Cyclophosphamide

Drug: Docetaxel

Drug: 5-Fluorouracil

Drug: Pertuzumab

Drug: Doxorubicin

Drug: Epirubicin

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Trastuzumab Emtansine

Primary Outcome(s)

Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation [Time Frame: Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.]

Invasive Disease-Free Survival (IDFS) in the Overall Population [Time Frame: First participant randomized up to approximately 7.5 years]

Secondary Outcome(s)

Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time [Time Frame: First participant randomized up to approximately 7.5 years.]

Distant Recurrence-Free Interval (DRFI) [Time Frame: Baseline up to approximately 70 months]

EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score [Time Frame: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18]

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score [Time Frame: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18]

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 start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above.]

Disease-Free Survival (DFS) [Time Frame: Baseline up to approximately 70 months]

Percentage of Participants With Adverse Events [Time Frame: From randomization to approximately 7.5 years]

IDFS Plus Second Primary Non-Breast Cancer [Time Frame: Baseline up to approximately 70 months]

Overall Survival (OS) [Time Frame: First participant randomized up to approximately 7.5 years]

Secondary ID(s)

2012-004902-82

BO28407

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/01/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01966471