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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

NCT01966471

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: BO28407
  • SECONDARY ID: 2012-004902-82
  • NCT ID: NCT01966471

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab EmtansineKadcylaAnthracycline Followed by Trastuzumab Emtansine and Pertuzumab
TrastuzumabHerceptinAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
PertuzumabPerjetaAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
PaclitaxelAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
EpirubicinAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
DoxorubicinAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
DocetaxelAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
CyclophosphamideAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane
5-FluorouracilAnthracycline Followed by Trastuzumab, Pertuzumab, and Taxane

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.

Trial Arms

NameTypeDescriptionInterventions
Anthracycline Followed by Trastuzumab, Pertuzumab, and TaxaneActive ComparatorTrastuzumab 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
  • Pertuzumab
  • Paclitaxel
  • Epirubicin
  • Doxorubicin
  • Docetaxel
  • Cyclophosphamide
  • 5-Fluorouracil
Anthracycline Followed by Trastuzumab Emtansine and PertuzumabExperimentalTrastuzumab 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
  • Epirubicin
  • Doxorubicin
  • Cyclophosphamide
  • 5-Fluorouracil

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive Disease-Free Survival (IDFS) in the Overall Population
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description: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

Measure:IDFS Plus Second Primary Non-Breast Cancer
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description: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.
Measure:Disease-Free Survival (DFS)
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description: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).
Measure:Distant Recurrence-Free Interval (DRFI)
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description:DRFI is defined as time between randomization and first occurrence of distant breast cancer recurrence.
Measure:Overall Survival (OS)
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description:OS is defined as the time from randomization to death due to any cause.
Measure:Percentage of Participants With Adverse Events
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description:
Measure:Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
Time Frame:Baseline up to approximately 10 years
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 21, 2017