A Study of Atezolizumab with Neoadjuvant Anthracycline/NAB Paclitaxel Based Chemotherapy Compared with Placebo and Chemotherapy in Patients with Primary Invasive Triple-Negative Breast Cancer
- Conditions
- Triple-negative breast cancerMedDRA version: 20.0 Level: LLT Classification code 10039850 Term: Secondary malignant neoplasm of breast System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004734-22-GB
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 324
- Women or men aged >= 18 years
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Histologically documented triple-negative breast cancer (TNBC) (negative human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PgR]). HER2 negativity will be defined by central laboratory assessment using in situ hybridization or immunohistochemistry (IHC) assays per American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) criteria and ER/PgR negativity will be defined by central laboratory assessment using IHC per ASCO/CAP criteria. Central laboratory assessment will occur prior to randomization.
- Patients with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as TNBC.
- Confirmed tumor programmed death-ligand 1 (PD-L1) evaluation as documented through central testing of a representative tumor tissue specimen
- Primary breast tumor size of > 2 cm by at least one radiographic or clinical measurement
- Stage at presentation: cT2 cT4, cN0 cN3, cM0
- Patient agreement to undergo appropriate surgical management including axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment
- Baseline left ventricular ejection fraction >= 53% measured by echocardiogram or multiple-gated acquisition scans
- Adequate hematologic and end-organ function
- Representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks (preferred) or at least 20 unstained slides, with an associated pathology report documenting ER, PgR, and HER2 negativity
- Women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or have undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating eggs.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
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 292
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32
- Prior history of invasive breast cancer
- Stage IV (metastatic) breast cancer
- Prior systemic therapy for treatment and prevention of breast cancer
- Previous therapy with anthracyclines or taxanes for any malignancy
- History of ductal carcinoma in situ (DCIS), except for patients treated exclusively with mastectomy >5 years prior to diagnosis of current breast cancer
- History of pleomorphic lobular carcinoma in situ (LCIS), except for patients surgically managed >5 years prior to diagnosis of current breast cancer (note that patients with nonpleomorphic LCIS [either untreated or treated with surgery] are allowed)
- Bilateral breast cancer
- Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
- Axillary lymph node dissection prior to initiation of neoadjuvant therapy
- History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of >90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, DCIS, or Stage I uterine cancer
- Cardiopulmonary dysfunction
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
- Known allergy or hypersensitivity to the components of the formulations of atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or pegfilgrastim
- Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type I diabetes mellitus, and only dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or vitiligo (e.g., patients with psoriatic arthritis are excluded)
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Positive HIV test at screening
- Active hepatitis B and hepatitis C virus infection
- Active tuberculosis
- Severe infections within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, except prophylactic antibiotics
- Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
- Prior allogeneic stem cell or solid organ transplantation
- Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method