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Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer (BOLD-1)

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ClinicalTrials.gov Identifier: NCT02625441
Recruitment Status : Recruiting
First Posted : December 9, 2015
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Heikki Joensuu, Helsinki University Central Hospital

Tracking Information
First Submitted Date  ICMJE December 5, 2015
First Posted Date  ICMJE December 9, 2015
Last Update Posted Date August 28, 2018
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2017)
Invasive disease-free survival [ Time Frame: 7 years ]
Time from the date of randomization to cancer recurrence or death.
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
Invasive disease-free survival [ Time Frame: 7 years ]
Change History Complete list of historical versions of study NCT02625441 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2018)
  • Overall survival [ Time Frame: 7 years ]
    Time from the date of randomization to death.
  • Distant disease-free survival [ Time Frame: 7 years ]
    Time from the date of randomization to distant recurrence of cancer or to death.
  • Left ventricle ejection fractions [ Time Frame: 3 years ]
    Cardiac ejection fraction measured with echocardiography or isotope cardiography.
  • Adverse events of the treatments [ Time Frame: 7 years ]
    Adverse events considered to be related to the treatments.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
  • Overall survival [ Time Frame: 7 years ]
  • Distant disease-free survival [ Time Frame: 7 years ]
  • Left ventricle ejection fractions [ Time Frame: 3 years ]
  • Adverse events of the treatments [ Time Frame: 7 years ]
  • Quality of life [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Pertuzumab
    Pertuzumab 420 mg i.v. 3-weekly for 3 cycles
    Other Name: Perjeta
  • Drug: Trastuzumab
    Trastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year
    Other Name: Herceptin
Study Arms  ICMJE
  • Experimental: Short anti-HER2 treatment
    Pertuzumab 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
    Intervention: Drug: Pertuzumab
  • Active Comparator: Standard anti-HER2 treatment
    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; Trastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year
    Intervention: Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 8, 2015)
1366
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Heikki Joensuu, M.D. 094711 ext +358 heikki.joensuu@hus.fi
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02625441
Other Study ID Numbers  ICMJE FBCG-01-2015
2015-002323-25 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Heikki Joensuu, Helsinki University Central Hospital
Study Sponsor  ICMJE Helsinki University Central Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Heikki Joensuu, M.D. Helsinki University Central Hospital
PRS Account Helsinki University Central Hospital
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP