eoadjuvant therapy in TRIPle negative breast cancer with antiPDL1

• Conditions: Women with a diagnosis of invasive unilateral locally advanced or inflammatory, triple negative (HER2-negative and ER-negative and PgRnegative) breast cancer of high proliferation or grade suitable for neoadjuvant Therapy.; MedDRA version: 18.1Level: LLTClassification code 10006196Term: Breast cancer NOS stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.1Level: PTClassification code 10006201Term: Breast cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.1Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.1Level: LLTClassification code 10021975Term: Inflammatory breast cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005017-23-ES
• Lead Sponsor: Fondazione Michelangelo - Avanzamento dello studio e cura dei tumori

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-25
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 272

Inclusion Criteria

1.Female patients aged 18 years or older
2.Locally advanced or inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant Treatment
3.Histologically confirmed unilateral breast cancer with invasive ductal histology
4.HER2 negative disease (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)
5.Negative estrogen receptor (ER) and progesterone receptor (PgR), both < 1% locally assessed
6.Representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for confirmation of HER2, ER and PgR eligibility, for assessment of PDL-1 expression and for further exploratory biomarker evaluation is mandatory. Note: FFPE tumor blocks are also mandatory after the first cycle of therapy; surgery tissue (residual tumor or tumor bed in case of pCR) is also mandatory
7.ECOG performance status 0 or 1
8.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
9.Willing and able to comply with the protocol
10.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), at the end of adjuvant chemotherapy and once a year for 2 years during follow-up
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 272
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 272

Exclusion Criteria

1.Evidence of bilateral breast cancer or metastatic disease (M1)
2.Cases with an histology different from invasive ductal NOS of high proliferation or grade
3.Patients with HER2-positive disease according to ASCO/CAP guidelines 2013 (defined as IHC 3+ or ISH positive according to the Guidelines) are considered not eligible for the study
4.Pregnant or lactating women.
5.Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy
6.Previous investigational treatment for any condition within 4 weeks of randomization date
7.Administration of a live,attenuated vaccine within 4 weeks before cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
8.Previous or concomitant invasive malignancy of any other type or previous invasive breast cancer or curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally 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
11.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
12.Patients with prior allogeneic stem cell or solid organ transplantation
13.History of autoimmune disease including, but not limited to, systemic lupus erythematosus, heumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener?s granulomatosis, Sjögren?s syndrome, Bell?s palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
14.History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography 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. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen [anti-HBc] test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay (PCR) is negative for HCV RNA
17.Active tuberculosis
18.Severe infections within 4 weeks prior to cycle 1 Day 1, including, but not limited to, ospitalization for complications of infection, bacteremia, or severe pneumonia. Signs or symptoms of significant infection within 2 weeks prior to cycle 1 Day 1
19.Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
20.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 cycle 1 Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or transient ischemic attack (TIA) within 6 months prior to cycle 1 Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias
21.Patients with a history of uncontrolled seizures, central nervous system

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified