Trial Title:
Diagnostic HER2DX-guided Treatment for patIents wIth Early-stage HER2-positive Breast Cancer
NCT ID:
NCT06446882
Condition:
HER2-positive Breast Cancer
Early-stage Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
Personalized treatment according to molecular diagnosis with HER2DX
Description:
Patients with HER2DX high-risk disease:
- Neoadjuvant treatment:
- High HER2DX pCR score: paclitaxel per 12 weeks + trastuzumab +/- pertuzumab per
4-5 cycles.
- Medium HER2DX pCR score: carboplatin + paclitaxel per 12-18 (or docetaxel per
4-6 cycles) + trastuzumab +/- pertuzumab per 4-7 cycles.
- Low HER2DX pCR score: standard of care neoadjuvant CT regimens and HER2
blockade at the investigator's choice.
- Adjuvant treatment:
- pCR at surgery; Trastuzumab +/- pertuzumab up to a total of 18 cycles
(including neoadjuvant and adjuvant therapy).
- No pCR at surgery: T-DM1 per 14 cycles.
Patients with HER2DX low-risk disease:
- Neoadjuvant treatment: paclitaxel per 12 weeks + trastuzumab +/- pertuzumab per 4-5
cycles.
- Adjuvant treatment will be according to the pCR status at surgery:
- pCR at surgery: trastuzumab or no adjuvant treatment.
- No pCR at surgery: trastuzumab or T-DM1.
Arm group label:
Arm B: Personalized treatment according to molecular diagnosis with HER2DX
Intervention type:
Other
Intervention name:
Treatment by physician´s choice, blinded to the diagnostic HER2DX test results
Description:
Patients randomized in ARM A will be treated with standard of care neoadjuvant CT
regimens and HER2 blockade at the investigator's choice validated by national and/or
international guidelines.
Arm group label:
Arm A: Treatment by physician´s choice without the diagnostic test results
Summary:
The primary goal of the DEFINITIVE trial is to demonstrate the effectiveness of the
HER2DX diagnostic assay in enhancing the management of patients with early-stage HER2-
positive breast cancer.
Patients randomized to arm A will receive adjuvant treatment by physician´s choice,
blinded to the diagnostic HER2DX test results. Patients randomized to Arm B will receive
personalized treatment according to HER2DX results.
Detailed description:
This is an international, multicenter, prospective, randomized, two-arm, open-label,
phase III study to evaluate the HRQoL, safety, efficacy, and economical costs of using
HER2DX in patients with stage II to IIIA HER2-positive breast cancer, suitable for
neoadjuvant therapy.
A dual primary endpoint with an according multiple testing procedure is defined in this
study. First, the study will evaluate superiority in quality of life using i) the GHS
scale from the EORTC QLQ-C30 questionnaire version 3.0 and ii) the score from the FACIT
Fatigue Scale.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed informed consent must be obtained prior to any trial-specific procedure.
Note: Candidate patients in France must be affiliated to a Social Security System
(or equivalent).
2. Male/female patients who are at least 18 years of age on the day of signing informed
consent.
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. Eligible for any of the following drugs: taxane, carboplatin, trastuzumab,
pertuzumab and T-DM1 therapy.
5. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the
breast untreated and recently diagnosed.
6. Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 as determined by AJCC staging
system, 8th edition (specifically in accordance with Anatomic Stage group rules).
Note: Axillary lymph node status must be assessed by fine needle biopsy or core
biopsy. This procedure at screening will be omitted if there is no suspicion for
positive axillary lymph node(s) radiographically or if a pathological report of
suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is
available prior to the screening period.
7. Absence of distant metastasis (i.e., cM0).
8. Patients with multifocal tumors (more than one mass confined to the same quadrant as
primary tumor) are eligible provided at least one focus is sampled and locally
confirmed as HER2-positive.
9. Patients with multicentric tumors (multiple tumors involving more than one quadrant)
are eligible provided all discrete lesions are sampled and locally confirmed as
HER2-positive.
Note: In patients with multifocal or multicentric breast cancer, the largest lesion
should be measured to determine T stage and to performe the HER2DX test.
10. HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive
as per most recent ASCO- CAP guideline according to the local laboratory as
determined on the most recently analyzed tissue sample.
11. ER/PR status determined local based on pretreatment breast biopsy material according
to the most recent ASCO/CAP guidelines.
12. Candidates for neoadjuvant treatment.
13. Patient agreement to undergo appropriate surgical management, including axillary
lymph node surgery and partial or total mastectomy, after completion of neoadjuvant
treatment
14. Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram
(ECHO) or multiple-gated acquisition (MUGA) scans.
15. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary
tumor in the breast for diagnostic HER2DX test. The tumor tissue should be of good
quality based on total and viable tumor content and must be evaluated centrally for
quality prior to enrollment. Archival tumor tissue or ex professo biopsy are
acceptable.
16. Adequate hematologic and end-organ function.
17. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods, and agreement to refrain
from donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of
< 1% per year during the treatment period, 6 months after the final dose of
doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after
the final dose of paclitaxel, and 7 months after the final dose of trastuzumab,
pertuzumab, or T-DM1, whichever occurs last. Women must refrain from donating
eggs during this same period.
- A woman is of childbearing potential if she is postmenarcheal, has not reached
a postmenopausal state (> 12 continuous months of amenorrhea with no identified
cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus). The definition of childbearing potential
may be adapted for alignment with local guidelines or requirements.
- Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, copper intrauterine devices,
hormonal contraceptives that inhibit ovulation, and hormone-releasing
intrauterine devices in women with hormone receptor-negative tumors only; the
use of hormonal contraceptives and hormone releasing intrauterine devices are
prohibited in women with hormone receptor-positive tumors.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception.
18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as defined
below:
- With a female partner of childbearing potential who is not pregnant, men who
are not surgically sterile must remain abstinent or use a condom plus an
additional contraceptive method that together result in a failure rate of < 1%
per year during the treatment period and for 6 months after the final dose of
doxorubicin and/or cyclophosphamide, 6 months after the final dose of
paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or
T-DM1, whichever occurs last. Men must refrain from donating sperm during this
same period. Male patients are encouraged to seek advice regarding
cryoconservation of sperm prior to commencing study treatment because of the
possibility of infertility with CT.
- With a pregnant female partner, men must remain abstinent or use a condom
during the treatment period and for 6 months after the final dose of
doxorubicin and/or cyclophosphamide, 6 months after the final dose of
paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or
T-DM1, whichever occurs last to avoid exposing the embryo.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
1. Stage IV (metastatic) breast cancer.
2. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab,
carboplatin, T-DM1, docetaxel or paclitaxel.
3. Patients with synchronous bilateral invasive breast cancer.
4. Prior systemic therapy for treatment of breast cancer.
5. Ulcerating or inflammatory breast cancer.
6. Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph
nodes.
7. Sentinel lymph node procedure or axillary lymph node dissection prior to initiation
of neoadjuvant therapy.
8. Patients with a history of previous breast cancer are excluded. Patients with a
history of any other cancers (except non-melanoma skin cancer or carcinoma in situ
of the cervix), unless in complete remission with no therapy for a minimum of 3
years are excluded. For patients with a history of other non-breast
cancerscancerscancers within 3 years and considered of low risk of recurrence per
investigator's judgment (for example, papillary thyroid cancer treated with
surgery), eligibility is to be discussed with the Sponsor.
9. Cardiopulmonary dysfunction as defined by any of the following prior to
randomization:
- History of congestive heart failure of any classification.
- Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia
not controlled by adequate medication, severe conduction abnormality, or
clinically significant valvular disease.
- High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate
> 100/min at rest, significant ventricular arrhythmia [ventricular
tachycardia], or higher-grade atrioventricular [AV]-block [second degree
AV-block Type 2 [Mobitz 2] or third-degree AV-block]).
- Significant symptoms (Grade > 1) relating to left ventricular dysfunction,
cardiac arrhythmia, or cardiac ischemia.
- Myocardial infarction within 12 months prior to randomization.
- Evidence of transmural infarction on ECG.
- Requirement for oxygen therapy.
- Dyspnea at rest.
10. Major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment or anticipation of need for a major surgical procedure
during the Study.
11. Severe infection within 4 weeks prior to initiation of Study treatment, including
but not limited to hospitalization for complications of infection, bacteremia, or
severe pneumonia.
12. History of significant co-morbidities that, in the judgment of the investigator, may
interfere with the conduction of the Study, the evaluation of response, or with
consent procedure.
13. Pregnancy or breastfeeding, or intention of becoming pregnant during Study treatment
or within 6 months after the final dose of paclitaxel, or 7 months after the final
dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last.
Note: Women of childbearing potential must have a negative serum pregnancy test
result within 7 days prior to initiation of Study treatment.
14. Persons deprived of their liberty or under protective custody or guardianship.
15. Patients unwilling or unable to comply with the medical follow-up required by the
trial because of geographic, familial, social, or psychological reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
July 2024
Completion date:
November 2028
Lead sponsor:
Agency:
Fundacio Clinic Barcelona
Agency class:
Other
Collaborator:
Agency:
SOLTI Breast Cancer Research Group
Agency class:
Other
Collaborator:
Agency:
Austrian Breast & Colorectal Cancer Study Group
Agency class:
Other
Collaborator:
Agency:
UNICANCER
Agency class:
Other
Collaborator:
Agency:
Westdeutsche Studiengruppe GmbH (WSG)
Agency class:
Other
Collaborator:
Agency:
Istituto Oncologico Veneto IRCCS
Agency class:
Other
Collaborator:
Agency:
Istituto Europeo di Oncologia
Agency class:
Other
Collaborator:
Agency:
Sheba Medical Center
Agency class:
Other
Collaborator:
Agency:
University College Cork
Agency class:
Other
Collaborator:
Agency:
University of Padova
Agency class:
Other
Source:
Fundacio Clinic Barcelona
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06446882
