Clinical Trials /

Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer

NCT02625441

Description:

This randomized clinical trial compares two systemic treatments for HER2-positive breast cancer. The treatments are given either prior to breast surgery (as neoadjuvant treatment) or after breast surgery (as adjuvant treatment). In the investigational group (Group A) the study participants will receive a combination of two drugs directed at HER2 (two anti-HER2 antibodies) plus a chemotherapy agent (docetaxel) for a brief duration, and the patients allocated to the comparator group (Group B) will be treated with chemotherapy plus one anti-HER2 treatment (trastuzumab) for one year.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer
  • Official Title: A Randomized Phase III Study Comparing Trastuzumab, Pertuzumab Plus Docetaxel (TPD) Followed by 3 Cycles of Chemotherapy to the Current Standard Regimen as the Treatments of Early Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: FBCG-01-2015
  • SECONDARY ID: 2015-002323-25
  • NCT ID: NCT02625441

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PertuzumabPerjetaShort anti-HER2 treatment
TrastuzumabHerceptinStandard anti-HER2 treatment

Purpose

This randomized clinical trial compares two systemic treatments for HER2-positive breast cancer. The treatments are given either prior to breast surgery (as neoadjuvant treatment) or after breast surgery (as adjuvant treatment). In the investigational group (Group A) the study participants will receive a combination of two drugs directed at HER2 (two anti-HER2 antibodies) plus a chemotherapy agent (docetaxel) for a brief duration, and the patients allocated to the comparator group (Group B) will be treated with chemotherapy plus one anti-HER2 treatment (trastuzumab) for one year.

Detailed Description

      In this study, patients who have been diagnosed with HER2-positive early breast cancer will
      be randomly allocated in a 1:1 ratio to receive either three 3-weekly cycles of trastuzumab,
      pertuzumab and docetaxel (TPD) for a total duration of 9 weeks, followed by three further
      cycles of chemotherapy (Group A) or three 3-weekly cycles of trastuzumab and docetaxel (TD)
      followed by three further cycles of chemotherapy and single-agent anti-HER2 antibody
      treatment to complete one year of anti-HER2 treatment (Group B). These systemic treatments
      may be administered either prior to breast surgery (as neoadjuvant treatment) or after breast
      surgery (as adjuvant treatment). The study participants are required to have histologically
      verified breast cancer with a moderate to high risk for breast cancer recurrence despite
      macroscopically complete surgery for the breast tumor. The moderate/high risk of breast
      cancer recurrence is defined by presence of cancer in the axillary lymph nodes, or if the
      axillary lymph nodes do not contain cancer, by presence of a tumor larger than one centimeter
      in the breast. The study patients are followed up during the study treatments and after their
      completion with physical examination, blood tests, cardiac tests and, whenever indicated,
      with imaging. Approximately 700 patients will be randomly allocated to each of the two
      groups. The study hypothesis is that the regimen containing TPD may be more effective than
      the Group B treatment despite its brief duration.
    

Trial Arms

NameTypeDescriptionInterventions
Short anti-HER2 treatmentExperimentalPertuzumab 840 mg, i.v., then 420 mg i.v., 3-weekly for 3 cycles; Trastuzumab 8 mg/kg, i.v., then 6 mg/kg, 3-weekly for 3 cycles; Docetaxel 75 mg/m2, i.v., 3-weekly for 3 cycles
  • Pertuzumab
Standard anti-HER2 treatmentActive ComparatorTrastuzumab 8 mg/kg, i.v., then 6 mg/kg, 3-weekly for 3 cycles; Docetaxel 75 mg/m2, i.v., 3-weekly for 3 cycles; Trastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has provided a written informed consent prior to study-specific screening
             procedures, with the understanding that she has the right to withdraw from the study
             at any time, without prejudice.

          -  Woman > 18 years of age.

          -  Histologically confirmed invasive breast cancer.

          -  HER2-positive breast cancer (preferably assessed with in situ hybridization; CISH,
             FISH or SISH; if not available with immunohistochemistry 3+)

          -  A high risk of breast cancer recurrence with one of the following: i) Pathological N0
             with the longest invasive tumor diameter >10 mm; ii) Histologically confirmed regional
             node positive disease

        Exclusion Criteria:

          -  Presence of distant metastases.

          -  Inflammatory breast cancer.

          -  Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure,
             symptomatic coronary artery disease and cardiac arrhythmia not well controlled with
             medication) or myocardial infarction within the last 12 months.

          -  Left ventricular ejection fraction less than 50% (or under the institutional normal
             reference range) assessed by echocardiography or isotope cardiography.

          -  ER and HER-2 status (via in situ hybridization or immunohistochemistry) not
             determined.

          -  The WHO performance status > 1.

          -  Pregnant or lactating women.

          -  Women of childbearing potential unless using a reliable and appropriate contraceptive
             method. Women must have been amenorrheic for at least 12 months prior to study entry
             to be considered postmenopausal and to have no childbearing potential. Women of
             childbearing potential (menstruating within 12 months of study entry), or with no
             hysterectomy and age < 55, must have a negative pregnancy test at baseline.

          -  Randomization more than 12 weeks after the date of breast surgery.

          -  Organ allografts with immunosuppressive therapy required.

          -  Major surgery (except breast surgery) within 4 weeks prior to study treatment start,
             or lack of complete recovery from the effects of major surgery.

          -  Participation in any investigational drug study within 4 weeks preceding treatment
             start.

          -  Patients with a history of uncontrolled seizures, central nervous system disorders or
             psychiatric disability judged by the investigator to be clinically significant
             precluding study participation.

          -  Multifocal breast cancer when the largest cancer focus is not HER2-positive.

          -  History of another malignancy or contralateral invasive breast cancer within the last
             five years except cured basal cell carcinoma of skin or carcinoma in situ of the
             uterine cervix (exception: patients with bilateral HER2-positive breast cancer are
             eligible).

          -  One or more of the following: Blood hemoglobin < 10.0 g/dL, neutrophils < 1.5 x 109/L;
             platelet count < 120 x 109/L; Serum/plasma creatinine > 1.5 x Upper Limit of Normal
             (ULN); Serum/plasma bilirubin > ULN; Serum/plasma ALT and/or AST > 1.5 x ULN;
             Serum/plasma alkaline phosphatase > 2.5 x ULN

          -  Serious uncontrolled infection or other serious uncontrolled concomitant disease.

          -  Unwilling or unable to comply with the protocol for the duration of the study.

          -  History of hypersensitivity to the investigational products or to drugs with similar
             chemical structures.

          -  Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by CTCAE version
             4, unless related to mechanical etiology.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive disease-free survival
Time Frame:7 years
Safety Issue:
Description:Time from the date of randomization to cancer recurrence or death.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:7 years
Safety Issue:
Description:Time from the date of randomization to death.
Measure:Distant disease-free survival
Time Frame:7 years
Safety Issue:
Description:Time from the date of randomization to distant recurrence of cancer or to death.
Measure:Left ventricle ejection fractions
Time Frame:3 years
Safety Issue:
Description:Cardiac ejection fraction measured with echocardiography or isotope cardiography.
Measure:Adverse events of the treatments
Time Frame:7 years
Safety Issue:
Description:Adverse events considered to be related to the treatments.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Helsinki University Central Hospital

Trial Keywords

  • Breast cancer
  • docetaxel
  • pertuzumab
  • trastuzumab
  • HER2

Last Updated

February 12, 2020