Breast Cancer Breast Ductal Carcinoma
Conditions
Interventions
Subjects will undergo screening tests and assessments to determine eligibility,
and those eligible for the study will be randomised to a treatment arm in a 2:1
ratio:
Arm A:
Nivolumab 360mg + pac
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Participants must have histologically confirmed unilateral invasive breast carcinoma, with the following characteristics (i, ii, iii): i) Localized invasive breast ductal carcinoma, confirmed by the local pathologist, that includes T1c-T2, clinical node stage (cN)1-cN2, or T3 T4, cN0-cN2. Inflammatory breast cancer is allowed. ii) Participants must have ER+, HER2- BC meeting below characteristics (1,2): (1)ER+ breast cancer and with or without progesterone-receptor (determined by central laboratory as defined in the relevant American Society of Clinical Oncology [ASCO]-College of American Pathologists [CAP] Guidelines). (2)HER2- breast cancer tested in a local laboratory defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+, or 2+ (determined by local laboratory as defined in the relevant ASCO- CAP Guidelines). iii)Participant must have Protocol-specified disease grade 2 or 3 according to the most recent ASCO-CAP guidelines. • Participant must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1. • Participants provide tumor tissue at baseline (collected
Exclusion criteria
Exclusion criteria: • Women who are breastfeeding • Participants who are pregnant or expecting to conceive or father children during the study, starting with the screening visit through 12 months for patients who receive cyclophosphamide, or 7 months for patients who do not receive cyclophosphamide, after the last dose of study treatment. • The following Breast Cancer (BC) characteristics: - Ipsilateral invasive BC, Inoperable BC, Multicentric BC, Bilateral invasive BC, ipsilateral ductal carcinoma in situ treated with radiation, or contralateral invasive BC, at any time. - Definitive clinical or radiologic evidence of metastatic disease. - Any of the following clinical lymph node staging: cN3, cN3a, cN3b, or cN3c - History of ductal carcinoma in situ - History of pleomorphic lobular carcinoma in situ - Evidence of ER- BC - Undergone excisional biopsy of the primary tumour and/or axillary lymph nodes or has undergone sentinel lymph node biopsy • Patients with >= Grade 1 peripheral neuropathy. • Patients with an active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. • Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. • Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome (AIDS). • Prior malignancy active within the previous 3 years, except for locally curable cancers that have been apparently cured. • Participants with serious or uncontrolled medical disorders. • Other non-malignant systemic disease that would preclude the participant from receiving study treatment or would prevent required follow-up. • Active infection or chronic infection requiring chronic suppressive antibiotics. • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function. • Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. • Any treatment, local or systemic, including prior chemotherapy, Endocrine Therapy (ET), targeted therapy, and/or radiation therapy for the currently diagnosed BC prior to enrollment. • Concurrent use of hormone replacement therapy, hormonal contraception or any other estrogen-containing medication. • Surgical axillary staging procedure prior to enrollment (with the exception of fine-needle aspiration or core biopsy). • Surgical excisional biopsy of primary tumour. •
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event Free Survival (EFS) means the length of time a patient lives with their cancer from the point of diagnosis or start of treatment without it getting worse. It is a good indicator of how well the treatment is working and is often used as a standard measure in clinical trials. EFS will be defined as the time from randomization to disease progression that: precludes definitive surgery, results in a local or distant recurrence, results in a second primary malignancy, or results in death due to any cause, whichever occurs first. Pathological Complete Response (pCR) is defined as no invasive residual disease in breast and lymph nodes, this will be determined by a local pathologist. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives of the study are: - to compare Overall Survival (OS) for Arm B vs Arm C participants - to compare Progression Free Survival (PFS) for Arm B vs Arm C - to assess Objective Response Rate (ORR) and Complete Response Rate - to assess Duration of Response (DOR) - to assess Time to Response (TTR) - to assess Time to Death or Distant Metastases (TTDM) All of the above assessments will be performed per RECIST 1.1 using a blinded independent committee review (BICR) Definitions: Progression free survival or PFS is defined as the length of time a patient lives with their cancer from the point of diagnosis or start of treatment without it getting worse. Overall survival or OS is defined as the length of time a patient lives with their cancer from the point of diagnosis or start of treatment. Objective response rate or ORR refers to a proportion of patients with reduction in tumour burden of a predefined amount Duration of response or DOR is defined as the time from documentation of tumour response to disease progression Time to response (TTR) Time to response is defined as the time, in months, from randomisation to the first objective documentation of partial response (PR- at least a 30% reduction in measurable tumour size) or better assessed per BICR. TTDM is defined as the time from the date of randomisation until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field according to RECIST 1.1 | — |
Countries
Netherlands
Outcome results
None listed