TOUCH IBCSG 55-17: studio clinico randomizzato, multicentrico, in aperto di fase II per la valutazione di palbociclib neoadiuvante in associazione a terapia ormonale e blocco di HER2 rispetto a paclitaxel in associazione al blocco di HER2 per pazienti anziane affette da carcinoma mammario in stadio iniziale positivo ai recettori ormonali/HER2 positivo - NCT03644186

Studio Clinico

Patologia: Neoplasie della mammella

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Adiuvante/neoadiuvante

Criteri di inclusione: 

- Histologically confirmed invasive breast cancer, with the following characteristics:
- Early breast cancer with tumor size >1 cm (as measured by at least one of the required examination methods of clinical examination, mammography and ultrasonography); No clinical evidence of regional lymph node metastasis (N0), or, nodal involvement limited to clinically detectable metastasis to movable ipsilateral level I, II axillary lymph node(s) (N1); No evidence of metastasis (M0).
- Female aged 65 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Primary tumor must have positive estrogen receptor (ER) ≥10%
- Primary tumor must be HER2-positive (by IHC and/or ISH)
- Baseline LVEF ≥55% measured by Echocardiography (preferred) or MUGA scan
- Normal hematologic status: Absolute neutrophil count ≥1500/mm3 (1.5 × 109/L); Platelets ≥100 × 109/L; Hemoglobin ≥9 g/dL (≥90 g/L).
- Normal renal function: serum creatinine ≤1.5 ULN
- Normal liver function: Serum total bilirubin ≤1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 × ULN) is allowed; AST or ALT ≤2.5 × ULN; Alkaline phosphatase ≤2.5 × ULN.
- Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.
- The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
- The patient agrees in writing to make tumor (mandatory diagnostic core biopsy and surgical specimen) available for submission for central pathology review and to conduct translational studies as part of this protocol.

Criteri di esclusione: 

- Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) (T4 according to AJCC 8th edition cancer staging TNM)
- Inflammatory breast cancer
- Bilateral invasive breast cancer
- Received any prior treatment for primary invasive breast cancer
- Any active tumor of non-breast-cancer histology
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification ≥II), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
- Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
- Contraindications or known hypersensitivity to any of the trial medications or excipients
- Treatment with any investigational agents within 30 days prior to expected start of trial treatment
- Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection

Trattamento sperimentale: 

Palbociclib plus letrozole plus trastuzumab and pertuzumab

Trattamento di controllo: 

Paclitaxel plus trastuzumab and pertuzumab

Obiettivi primari dello studio: 

• Pathological complete response (pCR) [ Time Frame: Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped. ]
  Defined as absence of invasive tumour cells in the breast and in the axillary lymph nodes at the time of surgery (ypT0/ypTis ypN0) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual. The presence of in situ cancer after trial treatment in the absence of residual invasive disease constitutes a pCR.

Obiettivi secondari dello studio: 

• Pathological complete response (pCR) in the breast [ Time Frame: Assessed at the time of breast surgery within 30 days of completion of a treatment period of up to 16 weeks. All patients who are discontinued from treatment for any reason will be documented within 30 days after surgery. ]
  Defined as the absence of invasive tumour cells in the breast at the time of surgery (ypT0/ypTis) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual..
• Objective response [ Time Frame: Tumour assessments will be performed by ultrasound and mammography at screening (prior to start of treatment), and before surgery. Tumour measurements by caliper will be assessed at the same time points and at the end of cycle 2 (each cycle is 28 days). ]
  Defined as the number of patients with partial or complete response measured physically by caliper and by ultrasound and mammography. Response will be assessed using World Health Organisation tumour measurement and response criteria.
• Frequency of reported adverse events [ Time Frame: From the time informed consent is signed, during treatment and until 30 days after surgery. If there is no surgery, adverse events will be collected until 30 days after treatment stops. ]
  Defined by frequency of all grades for targeted adverse events, all grade 3 for non-targeted events and grade ≥2 for non-targeted events requiring medical attention according to CTCAE version 5. For each adverse event, the frequency of patients by worst grade of the adverse event will be summarized and tabulated by treatment.
• Rate of breast conserving surgery (BCS) [ Time Frame: Assessed at 35 months after randomization of the first patient. ]
  Defined as the number of patients undergoing BCS, divided by the number of patients in the assessable population (subset of the randomized population with RBsig status successfully determined who received at least 1 dose of medication).

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2017-005067-40

Data di inserimento: 09.04.2019

Data di aggiornamento: 20.02.2020

Promotore

International Breast Cancer Study Group (collaborators: Pfizer, Hoffmann-La Roche)

CRO

/

Principal Investigator ITALIA

IEO - Istituto Europeo di Oncologia, Milano

Riferimento: Prof. Marco Colleoni

Telefono: 0257489934

Email: marco.colleoni@ieo.it

Localita: Milano