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Trial record 1 of 1 for:    BO28407
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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01966471
First received: October 17, 2013
Last updated: May 30, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: Trastuzumab Emtansine Drug: Trastuzumab Drug: Pertuzumab Drug: Paclitaxel Drug: Epirubicin Drug: Doxorubicin Drug: Docetaxel Drug: Cyclophosphamide Drug: 5-Fluorouracil Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Invasive Disease-Free Survival (IDFS) in the Overall Population [ Time Frame: Baseline up to approximately 10 years ]
    IDFS is defined as time from randomization to occurrence of ipsilateral breast cancer recurrence, second primary invasive breast cancer, distant recurrence, or death due to any cause.

  • IDFS in the Node-Positive Subpopulation [ Time Frame: Baseline up to approximately 10 years ]
    IDFS is defined as time from randomization to occurrence of ipsilateral breast cancer recurrence, second primary invasive breast cancer, distant recurrence, or death due to any cause.


Secondary Outcome Measures:
  • IDFS Plus Second Primary Non-Breast Cancer [ Time Frame: Baseline up to approximately 10 years ]
    IDFS is defined as time from randomization to occurrence of ipsilateral breast cancer recurrence, second primary invasive breast cancer, distant recurrence, or death due to any cause plus second primary non-breast cancer, excluding non-melanoma skin cancers and carcinoma in situ of any site.

  • Disease-Free Survival (DFS) [ Time Frame: Baseline up to approximately 10 years ]
    DFS is defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS).

  • Distant Recurrence-Free Interval (DRFI) [ Time Frame: Baseline up to approximately 10 years ]
    DRFI is defined as time between randomization and first occurrence of distant breast cancer recurrence.

  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 10 years ]
    OS is defined as the time from randomization to death due to any cause.

  • 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) ]

Enrollment: 1846
Actual Study Start Date: January 31, 2014
Estimated Study Completion Date: January 31, 2024
Estimated Primary Completion Date: January 31, 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
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.
Drug: Trastuzumab
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).
Other Name: Herceptin
Drug: Pertuzumab
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).
Other Name: Perjeta
Drug: Paclitaxel
IV infusion of paclitaxel 80 mg/m^2 once weekly may be administered concurrently with trastuzumab in combination with pertuzumab for 12 weeks.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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: Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
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.
Drug: Trastuzumab Emtansine
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).
Other Name: Kadcyla
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 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: 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966471

  Show 341 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01966471     History of Changes
Other Study ID Numbers: BO28407
2012-004902-82 ( EudraCT Number )
Study First Received: October 17, 2013
Last Updated: May 30, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Polystyrene sulfonic acid
Doxorubicin
Liposomal doxorubicin
Epirubicin
Docetaxel
Pertuzumab
Taxane
Ado-trastuzumab emtansine
Cyclophosphamide
Trastuzumab
Fluorouracil
Paclitaxel
Albumin-Bound Paclitaxel
Maytansine
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017