Breast CancerPhase 3BOLD-1NCT02625441
Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer
A Phase 3 study testing Pertuzumab and Trastuzumab in people with Breast Cancer, run by Helsinki University Central Hospital at 1 site in Finland.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pertuzumab and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 516 participants
- Where
- 1 siteFinland
- Study dates
- Dec 2015to 1 Jun 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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 520 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.
- Conditions
- Breast Cancer
- Being tested
- Pertuzumab, Trastuzumab
- Keywords
- Breast cancer, docetaxel, pertuzumab, trastuzumab, HER2
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PertuzumabDrug
Also called Perjeta
Pertuzumab 420 mg i.v. 3-weekly for 3 cycles
TrastuzumabDrug
Also called Herceptin
Trastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year
| Study group | Role | What they receive |
|---|---|---|
| Short anti-HER2 treatment | Experimental | 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 Receives: Drug: Pertuzumab |
| Standard anti-HER2 treatment | Active comparator | 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 Receives: Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive disease-free survival
Time from the date of randomization to cancer recurrence or death.
Measured: 7 years
Secondary outcomes (4)
Overall survival
Time from the date of randomization to death.
Measured: 7 years
Distant disease-free survival
Time from the date of randomization to distant recurrence of cancer or to death.
Measured: 7 years
Left ventricle ejection fractions
Cardiac ejection fraction measured with echocardiography or isotope cardiography.
Measured: 3 years
Adverse events of the treatments
Adverse events considered to be related to the treatments.
Measured: 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2015 (estimated)
- Study startDec 2015
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 516 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Heikki Joensuu, Helsinki University Central Hospital
- Investigators
- Heikki Joensuu, M.D., Principal investigator, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02625441
- Sponsor's protocol ID
- FBCG-01-2015
- Other IDs
- 2015-002323-25, 2015
- Acronym
- BOLD-1
- Status last verified
- Feb 2025
- First submitted
- 5 Dec 2015
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02625441
- Acronym / sponsor ID
- BOLD-1 / FBCG-01-2015
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, docetaxel, pertuzumab, trastuzumab, HER2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 516 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 9 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 520 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Short anti-HER2 treatment | Experimental | Drug: PertuzumabPertuzumab 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 |
| Standard anti-HER2 treatment | Active comparator | Drug: TrastuzumabTrastuzumab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PertuzumabAlso: PerjetaPertuzumab 420 mg i.v. 3-weekly for 3 cycles | Drug | Short anti-HER2 treatment |
| TrastuzumabAlso: HerceptinTrastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year | Drug | Standard anti-HER2 treatment |
Primary outcome
Invasive disease-free survival
Time frame: 7 years
Time from the date of randomization to cancer recurrence or death.
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heikki Joensuu, M.D. principal investigator
Helsinki University Central Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pertuzumab and Trastuzumab in people with Breast Cancer, run by Helsinki University Central Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Invasive disease-free survival (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.