A Study of Neoadjuvant Nivolumab + Palbociclib + Anastrozole in Post-Menopausal Women and Men With Primary Breast Cancer
- Conditions
- CancerBreast Cancer
- Interventions
- Registration Number
- NCT04075604
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
A randomized multi-arm study evaluating the safety and efficacy of palbociclib and anastrozole with or without nivolumab in participants with ER+/HER2- breast cancer
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- Participants must have untreated, unilateral, histologically confirmed ER+, HER2- invasive breast cancer with primary tumor ≥2 cm in largest diameter (cT1-3) in one dimension by clinical or radiographic exam, for whom neoadjuvant endocrine monotherapy deemed to be a suitable therapy.
- Participants must be deemed eligible for surgery and must agree to undergo surgery after completion of neoadjuvant therapy and agree to provide tumor tissue at baseline, on-treatment, and at surgery.
- Women must have documented proof that they are not of childbearing potential.
- Participants must have a performance status (PS) ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- Participants who may have had any treatment, including radiotherapy, chemotherapy, and/or targeted therapy administered for the currently diagnosed breast cancer prior to enrollment or for whom upfront chemotherapy is clinically judged appropriate as optimal neoadjuvant treatment.
- Participants who have a history of or active, known or suspected autoimmune disease, or other syndrome that requires systemic steroids above physiological replacement dose or autoimmune agents for the past 2 years.
- Prior treatment with either ET or CDK4/6 inhibitors for Breast Cancer (BC) within 5 years or 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, or history of allergy, or hypersensitivity to study drug components
- Prior malignancy active within the previous 3 years or participants with serious or uncontrolled medical disorders.
- Personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), long or short QT syndrome, Brugada syndrome, or known history of corrected QT prolongation, Torsade de Pointes, or sudden cardiac arrest.
Other protocol-defined inclusion/exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ) Nivolumab - Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ Nivolumab - Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ) Anastrozole - Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ) Palbociclib - Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ Anastrozole - Arm C: Palbociclib+ANZ Anastrozole - Arm C: Palbociclib+ANZ Palbociclib - Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ Palbociclib -
- Primary Outcome Measures
Name Time Method The Number of Participants With Dose Limiting Toxicities (DLT) in the Safety Run-in Phase From first dose to 4 weeks after first dose The number of participants with dose limiting toxicities (DLTs) during the safety run-in phase. DLTS are defined as treatment emergent adverse events (TEAE) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 that occurs during the first 4 weeks (1 cycle) after treatment. Participants who withdraw from the study during the DLT evaluation period or have received less than 1 dose of nivolumab and 75% of accumulative doses of palbociclib of the cycle for reasons other than a DLT will not be considered as DLT-evaluable participants.
Residual Cancer Burden (RCB) 0-1 Rate in the Randomized Phase From randomization phase up to 5 treatment cycles (up to approximately 20 weeks) RCB 0-I rate is defined as the percentage of randomized participants who achieve RCB 0: no residual disease or RCB-I: minimal residual disease. RCB is a continuous index combining pathological measurements of primary tumor (size and cellularity) and nodal metastases (number and size) defined by a point system at surgery.
No participants continued to the randomized phase; trial was closed after completion of the Safety Run-in.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) From first dose up to approximately 6 months after first dose ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per investigator radiographic assessment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Breast Conserving Surgery (BCS) Rate From first dose up to approximately 6 months after first dose The percentage of participants who undergo breast conserving surgery (BCS) after completing the study treatments. Confidence interval based on the Clopper and Pearson method.
Pathological Complete Response (pCR) Rate From first dose up to approximately 6 months after first dose The percentage of participants with an absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Confidence interval based on the Clopper and Pearson method.
The Number of Participants Experiencing Adverse Events (AEs) From first dose to 30 days after last dose of study therapy (up to approximately 6 months) The number of participants experiencing adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Serious Adverse Events (SAEs) From first dose to 30 days after last dose of study therapy (up to approximately 6 months) The number of participants experiencing serious adverse events (SAEs). A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation From first dose to 30 days after last dose of study therapy (up to approximately 6 months) The number of participants experiencing adverse events (AEs) that lead to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Immune-Related Adverse Events (AEs) From first dose to 100 days after last dose of study therapy (up to approximately 8 months) The number of participants experiencing adverse events that are immune-related. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Deaths From first dose up to approximately 8 months The number of participants that have died during the study.
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests - SI Units From first dose to 30 days after last dose of study therapy (up to approximately 6 months) The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units.
TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of NormalThe Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests From first dose to 30 days after last dose of study therapy (up to approximately 6 months) The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units.
ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
Trial Locations
- Locations (31)
The Cancer Center At Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hematology-Oncology Associates Of Fredricksburg, Inc
🇺🇸Fredericksburg, Virginia, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Local Institution - 0011
🇧🇪Wilrijk, Antwerpen, Belgium
Local Institution - 0062
🇵🇷San Juan, Puerto Rico
University Cancer Blood Ctr
🇺🇸Athens, Georgia, United States
Local Institution - 0031
🇺🇸Whittier, California, United States
Local Institution - 0072
🇫🇷La Roche-sur-yon Cedex 9, France
Centre de Cancerologie du Grand Montpellier
🇫🇷Montpellier, France
H. Univ. Vall dHebron
🇪🇸Barcelona, Spain
Local Institution - 0037
🇪🇸Barcelona, Spain
Institut Claudius Regaud
🇫🇷TOULOUSE Cedex 9, France
Local Institution - 0071
🇨🇦Ottawa, Ontario, Canada
Local Institution - 0002
🇵🇷San Juan, Puerto Rico
Klinik Essen-Mitte
🇩🇪Essen, Germany
Local Institution - 0047
🇵🇷Monterrey Ponce, Puerto Rico
Local Institution - 0073
🇫🇷Creteil Cedex, France
Centre Leon Berard
🇫🇷Lyon Cedex 08, France
Hospital Universitario Virgen De La Victoria
🇪🇸Malaga, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp Univer 12 De Octubre
🇪🇸Madrid, Spain
Hospital Clinico Universitario De Valencia
🇪🇸Valencia, Spain
Northside Hospital,Inc.- Central Research Department
🇺🇸Atlanta, Georgia, United States
Local Institution - 0041
🇺🇸Florham Park, New Jersey, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Peninsula Cancer Institute
🇺🇸Newport News, Virginia, United States
Local Institution - 0005
🇦🇺Elizabeth Vale, South Australia, Australia
Breast Cancer Research Centre - WA
🇦🇺Nedlands, Western Australia, Australia
Local Institution
🇩🇪Saarbruecken, Germany
Local Institution - 0075
🇫🇷Bordeaux, France
Local Institution - 0019
🇫🇷Marseille Cedex 9, France