Breast cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Phesgo
Product Name: Trastuzumab/pertuzumab FDC
Pharmaceutical Form: Infusion
INN or Proposed INN: TRASTUZUMAB/PERTUZUMAB
Other descriptive name: Phesgo
Concentration unit: mg milligram(s)
Sponsors
Fundació Clínic per a la Recerca Biomèdica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer. 2. A participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment. 3. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 4. Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics: – HER2-positive status by local determination according to 2018 ASCO/CAP guidelines(1). – PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination. – Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component) – Tumor largest diameter =4 cm as defined by breast MRI. – No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible. – No evidence of distant metastasis (M0) by routine clinical assessment. 5. Patient must have known ER and PR status locally determined prior to study entry (2). 6. Eligible for taxane therapy 7. Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy. 8. Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer. 9. Breast cancer eligible for primary surgery 10. Have provided archival tumor tissue sample or newly obtained core. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are mandatory. Available pre-treatment FFPE core biopsy evaluable for PAM50 or possibility to obtain one. 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation. 12. Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol. 13. Have adequate organ function as defined in protocol. Specimens must be collected within 10 days prior to the start of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 2. Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer. 3. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel. 4. Clinical stage III or IV. 5. History of radiotherapy in the ipsilateral breast or axilla. 6. History of surgery of the ipsilateral axilla. 7. Bilateral invasive breast cancer. 8. Infiltrating lobular carcinoma. 9. Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast. 10. Patients who have undergone sentinel lymph node biopsy prior to study treatment. 11. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: – History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening. – History of documented congestive heart failure (New York Heart Association functional classification III-IV). – Documented cardiomyopathy. – Patient has a Left Ventricular Ejection Fraction (LVEF) 500 msec or conduction abnormality in the previous 12 months. 12. Has an active infection requiring systemic therapy. 13. Patients with a history of previous breast cancer are excluded. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years are excluded. For patients with a history of other non-breast cancers within 5 years and considered of very low risk of recurrence per investigator’s judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with Study Medical Monitor. 14. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required. 15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required. 16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 18. Is pregnant or breastfeeding or e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the possibility of omission of surgery and sentinel lymph node dissection in clinically low-risk HER2-positive breast cancer with high HER2 addiction and a complete response following standard neoadjuvant chemotherapy and dual HER2 blockade;Secondary Objective: 1. To assess measures of clinical benefit of both arms 2. Analyze the financial impact of the omission of breast cancer surgery. 3. To assess the effect of investigational treatment and standard treatment on patient reported outcomes (PROs). 4. To evaluate the safety and tolerability of investigational treatment and their corresponding standard treatment.;Primary end point(s): To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery. 3-years LR-IDFS rate defined as time from the first date of no disease (i.e., date of stereotaxic guided biopsy) to loco-regional recurrence. Loco-regional recurrence is defined as recurrence of breast cancer in the same breast parenchyma as the original primary lesion, the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast.;Timepoint(s) of evaluation of this end point: 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.1 To estimate the disease-free survival at 3years and 5-years of patients who achieve a complete response based on imaging (i.e. MRI) and a stereotaxic guided biopsy and omit loco-regional surgery following neoadjuvant chemotherapy and dual HER2 blockade. 1.2 To estimate the disease-free survival at 3years and 5-years of patients who do not achieve a complete response based on imaging (i.e. MRI) following neoadjuvant chemotherapy and dual HER2 blockade. 1.3 To compare the rate of pathological complete response (pCR) between the treatment groups by HR status. 2.1 To compare the cost in patients with and without breast cancer surgery, not only direct cost for hospitals/public health system, but also indirect cost for public system 3.1 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30), version 3. 3.2 EORTC QLQ-BR23 (breast cancer-specific questionnaire). 4.1 Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5, including dose reductions, delays and treatment discontinuations.;Timepoint(s) of evaluation of this end point: end to the study | — |
Countries
Spain
Contacts
Public ContactStudy coordinator
Fundació Clínic per a la Recerca Biomèdica
Outcome results
None listed