The purpose of this study is to see whether a combination of two different drugs - pembrolizumab and capecitabine - is safe, and if it might be effective in treating triple negative and hormone-refractory breast cancer. Pembrolizumab is a type of drug that contains an antibody. Antibodies are the part of your immune system that finds things that don't belong in your body, such as bacteria or viruses. The antibody in pembrolizumab finds and blocks a protein, which allows your immune system to target and destroy cancer cells. Pembrolizumab is Food and Drug Administration (FDA) approved for other types of cancer. It is not approved for breast cancer, meaning that it is an "experimental" or "investigational" treatment. Capecitabine is a type of chemotherapy pill that is a standard treatment and FDA-approved for breast cancer. It stops the cancer cells from being able to multiply.
PRIMARY OBJECTIVES: I. To evaluate the median progression-free survival (median PFS) for participants receiving pembrolizumab with capecitabine for the treatment of locally advanced or metastatic triple negative breast cancer (TNBC) and hormone-refractory metastatic breast cancer (MBC). SECONDARY OBJECTIVES: I. To describe the objective response rate (ORR) for participants receiving pembrolizumab with capecitabine for the treatment of locally advanced or metastatic TNBC and hormone-refractory MBC. II. To describe the safety and tolerability of the combination of pembrolizumab and capecitabine for the treatment of locally advanced or metastatic TNBC and hormone-refractory MBC. TERTIARY OBJECTIVES: I. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) through immunohistochemical (IHC) analysis. II. To assess circulating tumor DNA (ctDNA). III. To evaluate ORR and median-PFS using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). OUTLINE: Patients receive pembrolizumab intravenously (IV) on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Northwestern University
Chicago, Illinois, United States
Northwestern Lake Forest Hospital
Lake Forest, Illinois, United States
Median PFS (Median Progression-Free Survival)
To evaluate the median Progression-Free Survival (PFS) for participants receiving pembrolizumab with capecitabine for the treatment of locally advanced or metastatic TNBC and hormone-refractory MBC. PFS is defined as the length of time during and after the treatment that a patient does not experience progression. Progressive Disease (PD) as defined per RECIST 1.1 is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). PFS was analyzed using a Kaplan-Meier curve. For PFS, assumptions were that the addition of pembrolizumab would increase PFS to 5 months compared to historical control of 3 months.
Time frame: Approximately 20 months
Objective Response Rate (ORR)
The ORR is the percentage of patients whose cancer shrinks or disappears after treatment. Objective response rate was calculated based on the number of patients who had a Complete Response (CR) or a Partial Response (PR). CR and PR were measured according to RECIST v. 1.1 guidelines: * Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 9 Cycles (1 cycle = 21 days)
Incidence of Adverse Events
Determine the safety and tolerability of the combination of pembrolizumab and Capecitabine by evaluating the incidence of adverse events. All adverse events will be assessed using the National Cancer Institute Common Terminology Criteria 4.03 criteria (NCI CTCAE 4.03 criteria).
Time frame: Up to 2 years
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