eo-Adjuvant study with the PDL1-directed antibody in Triple Negative, Early High-Risk and Locally Advanced Breast Cancer undergoing treatment with nab-paclitaxel and carboplatin. NeoTRIPaPDL1 (Neoadjuvant therapy in TRIPle negative breast cancer with antiPDL1)

Phase 1

• Conditions: Women with a diagnosis of invasive unilateral locally advanced or inflammatory, triple negative (HER2-negative and ER-negative and PgR-negative) breast cancer of high proliferation or grade suitable for neoadjuvant therapy.; MedDRA version: 20.0 Level: LLT Classification code 10006196 Term: Breast cancer NOS stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10006201 Term: Breast cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10021975 Term: Inflammatory breast cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-05-11
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 272

Inclusion Criteria

1.Female patients aged 18 years or older with early high-risk (T1cN1; T2N1; T3N0) or locally advanced or inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant treatment
2.Histologically confirmed unilateral breast cancer with invasive ductal histology not otherwise specified (NOS) of high proliferation or grade
3.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.
4.Negative estrogen receptor (ER) and progesterone receptor (PgR), both < 1% locally assessed
5.Representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for confirmation of HER2, ER and PgR eligibility, for assessment of PD-L1 expression and for further exploratory biomarker evaluation is mandatory. Note: FFPE tumor blocks are also mandatory after the first cycle of therapy; tissue (residual tumor or tumor bed in case of pCR) is also mandatory at surgery
6.ECOG performance status 0 or 1
7.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
8.Willing and able to comply with the protocol
9.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
10.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 6 months after the last dose of study drug. 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, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide
Note: patients with no uterus do not need to be on contraception.
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 182
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

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)
4.Pregnant or lactating women.Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs&for women less than one year after the last menstrual cycle
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 & 5 months after the last dose.
8. Previous or concomitant invasive malignancy of any other type or previous invasive breast cancer. Patients with 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,to human albumin solution,hypersensitivity to platinum containing compounds
11.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
12.Patients with prior allogeneic stem cell or solid organ transplantation
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,&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&a positive hepatitis B core antigen [anti-HBc] test)are eligible.
a. Patients positive for hepatitis C virus(HCV)antibody are eligible only if polymerase chain reaction assay 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,hospitalization 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.Other serious illness/medical condition incl.:history of documented congestive cardiac failure;New York Heart Association 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 within 6 months prior to cycle 1 Day 1;poorly controlled hypertension(eg. systolic >180 mm Hg or diastolic

Study & Design

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