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 at high risk of rapid disease progression; MedDRA version: 20.0Level: LLTClassification code 10006283Term: Breast neoplasm malignant femaleSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005017-23-IT
• Lead Sponsor: FONDAZIONE MICHELANGELO ONLUS PER L'AVANZAMENTO DELLO STUDIO E LA CURA DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-04
• Last Update Posted: 2 August 2021

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 with 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 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
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 90 days 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

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 metastases
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. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and 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 C1D1 or anticipation that such a live attenuated vaccine will be required during the study or within 5 mos after the last dose of Atezo
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
11.Patients with prior allogeneic stem cell or solid organ transplantation
12.History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
13.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
14.Active tuberculosis
15.Other serious illness or medical condition including: 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
16.Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
17.Any of the following abnormal baseline hematological values:
White blood count (WBC) < 2.5 x 109/L; Absolute Neutrophil Count (ANC) < 1.5 ¿ 109/L; Lymphocyte count < 0.5 x 109/L; Platelet count < 100 ¿ 109/L;Hemoglobin (Hb) < 10 g/dL
18.Any of the following abnormal baseline laboratory tests
Serum total bilirubin > 1.5 ¿ ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome); Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 ¿ ULN;

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Compare Event Free Survival (EFS) in the 2 study arms from the time of randomization;Secondary Objective: •Compare the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery<br>•Compare clinical overall response (cOR) at the end of neo-adjuvant therapy.<br>•Compare Distant EFS (DEFS) from the time of randomization<br>•Compare overall survival from the time of randomization<br>•Evaluate tolerability of the treatment regimens in the different study arms<br>•Conduct molecular and clinical analyses to assess the presence of prognostic and/or predictive markers of benefit and/or resistance to the study regimens and to improve our understanding of breast cancer disease. <br>;Primary end point(s): Compare Event Free Survival (EFS) in the 2 study arms from the time of randomization;Timepoint(s) of evaluation of this end point: 7 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Compare the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery<br>•Compare clinical overall response (cOR) at the end of neo-adjuvant therapy.<br>•Compare Distant EFS (DEFS) from the time of randomization<br>•Compare overall survival from the time of randomization<br>•Evaluate tolerability of the treatment regimens in the different study arms<br>•Conduct molecular and clinical analyses to assess the presence of prognostic and/or predictive markers of benefit and/or resistance to the study regimens and to improve our understanding of breast cancer disease. <br>;Timepoint(s) of evaluation of this end point: 10 years