Pembrolizumab, Carboplatin and Docetaxel in Treating Patients with Stage I-III Triple-Negative Breast Cancer before Surgery

Status: Active

Description

This phase II trial studies how well pembrolizumab, carboplatin and docetaxel work in treating patients with stage I-III triple-negative breast cancer before surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and docetaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab, carboplatin and docetaxel before surgery may work better in treating stage I-III triple-negative breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Ability of participant to understand this study, and participant willingness to sign a written informed consent for this trial
  • Histologically confirmed stage I (T > 1 cm or cN+), II or III TNBC * The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor (ER) and progesterone receptor (PR) staining present in =< 10% of invasive cancer cells by immunohistochemistry (IHC). * HER2 negativity will be based on current American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines for HER2 testing
  • No previous definitive ipsilateral breast surgery for the current breast cancer
  • No previous chemotherapy, endocrine therapy, or radiation therapy with therapeutic intent for this cancer
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Evaluation of performance status is to be performed within 10 days prior to the start of study treatment
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Leukocytes >= 3,000/uL
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
  • Creatinine =< 1.5 mg/dL and/or creatinine clearance >= 60 mL/min
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN), OR direct bilirubin =< IULN for participants with total bilirubin levels > 1.5 x IULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 2 x IULN
  • International normalized ratio (INR) of coagulation OR prothrombin time (PT) OR activated partial thromboplastin time (aPTT) =< 1.5 x IULN, unless patient is receiving anticoagulant therapy. If patient is receiving anticoagulant therapy, PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Serum albumin >= 3.0 g/dL
  • Pretreatment lab values must be performed within 10 days of treatment initiation, and other baseline studies performed within 30 days prior to registration
  • Subjects should have breast and axillary imaging with breast magnetic resonance imaging (MRI) (preferred) or breast and axillary ultrasound within 30 days prior to treatment initiation
  • Subjects with clinically/radiologically abnormal axillary lymph nodes should have pathological confirmation of the disease with image-guided biopsy/fine needle aspiration
  • Subjects must already be enrolled in P.R.O.G.E.C.T. observational registry (HSC #12614)
  • Have provided archival breast tumor tissue sample, which should include a formalin-fixed paraffin-embedded (FFPE) block or 12 unstained slides (ten 5-micron uncharged slides and two 5-micron charged slides) from primary breast tumor and/or axillary lymph node. If adequate archival breast tumor specimen is not available, a newly obtained core biopsy of breast tumor should be performed for submission of tumor specimen
  • Staging to rule out metastatic disease is suggested for subjects with clinical stage III disease
  • Subjects with bilateral disease are eligible if they meet other eligibility criteria
  • Neuropathy: no baseline neuropathy grade > 2
  • Cardiac function: * Subjects should have left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multi-gated acquisition (MUGA) scan performed within 30 days prior to treatment initiation * Subjects with congestive heart failure are not eligible, nor are subjects with myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack within the past 12 months, uncontrolled hypertension (systolic blood pressure [BP] > 160 or diastolic BP > 90), uncontrolled or symptomatic arrhythmia, or grade 2 or greater peripheral vascular disease
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP), OR * A WOCBP who agrees to follow the contraceptive guidelines during the treatment period and for at least 120 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treated physician immediately

Exclusion Criteria

  • Current or anticipated use of other investigational agents while participating in this study
  • Subject has received chemotherapy, radiotherapy, or surgery for the treatment of breast cancer
  • Subject has metastatic disease
  • Subject has inflammatory breast cancer
  • Subjects with concomitant or previous malignancies within the last 5 years are excluded from the study * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ [DCIS], carcinoma in situ of the cervix) that have undergone potential curative therapy are not excluded
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, docetaxel, or other agents used in this study
  • Has severe hypersensitivity (>= grade 3) to pembrolizumab or any of its excipients
  • Subject has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
  • If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
  • Subject has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • Subject is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a history of (non-infectious) pneumonitis that required steroids, or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV)
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as detectable hepatitis C virus [HCV] ribonucleic acid [RNA]) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Subject is pregnant or breast feeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. There is a potential for congenital abnormalities and for this regimen to harm breastfeeding infants (if applicable)
  • Subject is a WOCBP who has had a positive urine pregnancy test within 24 hours prior to initiation of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Note: In the event that 24 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
  • Ejection fraction < 50% on echocardiogram (ECHO) or MUGA

Locations & Contacts

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu
University of Kansas Cancer Center-West
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu
Overland Park
University of Kansas Cancer Center-Overland Park
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu

Missouri

Kansas City
The University of Kansas Cancer Center-North
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu
Lee's Summit
The University of Kansas Cancer Center-Lee's Summit
Status: Active
Contact: Priyanka Sharma
Phone: 913-588-6029
Email: psharma2@kumc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the pathological complete response (pCR) rates with a neoadjuvant chemotherapy regimen of carboplatin and docetaxel (CbD) plus pembrolizumab in patients with stage I-III triple-negative breast cancer (TNBC).

SECONDARY OBJECTIVES:

I. To evaluate minimal residual disease (MRD) rate (residual cancer burden score of 0/1) with a neoadjuvant chemotherapy regimen of CbD plus pembrolizumab in patients with stage I-III TNBC.

II. To determine 3-year recurrence-free survival with a neoadjuvant chemotherapy regimen of CbD plus pembrolizumab in patients with stage I-III TNBC.

EXPLORATORY OBJECTIVES:

I. To evaluate markers of deoxyribonucleic acid (DNA) repair deficiency and/or tumor genomic instability as biomarkers of response to treatment.

II. To evaluate immune therapy response biomarkers (e.g. PD-L1 expression, gene expression signatures).

OUTLINE:

Patients receive carboplatin intravenously (IV) over 30 minutes, docetaxel IV over 60 minutes, pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Within 3-10 weeks, patients undergo surgery.

After completion of study treatment, patients are followed up at 30 days and every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Kansas Cancer Center

Principal Investigator
Priyanka Sharma

Trial IDs

Primary ID IIT-2017-NeoPACT
Secondary IDs NCI-2019-00379
Clinicaltrials.gov ID NCT03639948