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Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant (before surgery) treatment of HER2 positive early high-risk and locally advanced breast cancer.

Phase 1
Conditions
Women with a diagnosis of non-metastatic high-risk invasive unilateral, HER2-positive breast cancer.
MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2017-000981-31-DE
Lead Sponsor
Michelangelo Foundation
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Female
Target Recruitment
650
Inclusion Criteria

1. Female patients aged 18 years or older with early high-risk ((T1cN1; T2N1; T3N0) or locally advanced and inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant treatment. NB: those sites who perform axillary ultrasound guided-fine needle aspiration or core biopsy are allowed to enroll patients with T2N0 tumors (assessed by paplation and/or imaging) after a pathological confirmation of axillary malignancy;
2. Histologically confirmed unilateral invasive breast cancer;
3. HER2 positive disease according to ASCO/CAP current guidelines;
4. Known estrogen (ER) and progesterone receptor (PgR) status;
5. Availability of a representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for central confirmation of HER2 status, for assessment of ER, PgR, Ki67 and PD-L1 expression and for biomarker evaluation is mandatory. Note: the diagnostic biopsy of the breast lesion may have been taken before screening procedures start. If diagnostic sentinel node or node core biopsy is performed, an FFPE block should be made available, along with the tumor block of the primary tumor. An FFPE tumor block is also mandatory after the first cycle of therapy. Surgery tissue (residual tumor or tumor bed in case of pCR and axillary node material) is also mandatory;
6. Consent to the collection of blood samples mandatorily before starting neoadjuvant treatment, after the first cycle of therapy, at the end of neoadjuvant treatment (before surgery), 6 months after surgery and at the end of all treatments;
7. ECOG performance status 0 or 1;
8. For women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drugs. Abstinence is only acceptable if it is in line with 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. Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices;
9. Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures;
10. Willing and able to comply with the protocol.
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 250

Exclusion Criteria

1. Evidence of bilateral breast cancer or metastatic disease (M1);2.Pts with HER2-NEG. defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either In Situ Hybridization (ISH) or other amplification tests done locally are considered not eligible for the study;3.Pregnant or lactating women. Documentation of a NEG. pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle;4.Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception as mentioned at point 8 of inclusion criteria;5.Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy.Bleeding tumours;6.Previous investigational treatment for any condition other than malignancy within 4 weeks or 5 half-lives of randomisation,whichever is longer;7.Administration of a live,attenuated vaccine within 4weeks before D1 or anticipation that such a live attenuated vaccine will be required during the study;8.Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results.Pts with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are eligible;9.Pre-existing motor or sensory neuropathy of grade>1 for any reason;10.History of severe allergic,anaphylactic,or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or hyaluronidase. History of any protocol anticancer agent or any of the excipients;11.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation;12.Pts with prior allogeneic stem cell or solid organ transplantation;13.History of autoimmune disease including,but not limited to,systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjörgren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis(see AppA for preexisting autoimmune diseases and immune deficiencies;14.History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest CT scan;15.Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;16.History of HIV infection, active hepatitis B (chronic or acute) or hepatitis C infection. (...);17.Active tuberculosis;18.Severe infections within 4 weeks prior to Day 1, including, but not limited to, hospitalisation for complications of infection, bacteriemia, or severe penumonia. Signs or symptoms of significant infection within 2weeks prior to Day 1;19.Received oral or IV antibiotics within 2weeks prior to Cycle 1 Day 1;20.Other serious illness or medical condition incl. but not limited to: history of documented congestive cardiac failure; New York Heart Association (NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal medication or unstable angina within 6 months prior to Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or TIA within 6 months prior to Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients wi

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
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