Pembrolizumab and Capecitabine in Treating Patients With Locally Advanced or Metastatic Triple Negative or Hormone-Refractory Breast Cancer That Cannot Be Removed by Surgery

NCT03044730 | Unknown Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 16B08STU00203215P30CA060553NCI-2017-00152
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Approximately 20 months

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  Up to 9 Cycles (1 cycle = 21 days)

• Incidence of Adverse Events

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, capecitabine)

EXPERIMENTAL

Patients receive pembrolizumab IV on day 1 and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (pembrolizumab, capecitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, capecitabine)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, capecitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically-confirmed unresectable, locally advanced or metastatic breast cancer that meets one of the following:
• Triple negative, defined as estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor receptor 2 (HER2) negative; HER2 negative defined as immunohistochemistry (IHC) 0 or 1+ or fluorescence in situ hybridization (FISH) negative
• Hormone-refractory breast cancer which denotes progression to endocrine therapy (e.g., tamoxifen, aromatase inhibitors, fulvestrant) unless contraindicated
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patients must have a life expectancy of \>= 90 days
• Patients must have baseline laboratory tests within the following parameters at least 4 weeks (28 days) prior to registration:
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Patients with documented HER2-positive metastatic disease are not eligible, even if their primary breast cancer was HER2-negative
• Patients who have received prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 2 weeks prior to registration; hormone therapy is permitted until registration
• Note: patients who received prior anti-PD-1, PD-L1 or PD-L2 agents are still eligible
• Patients who have not recovered from adverse events to grade 1 severity or lower due to agents administered more than 2 weeks earlier than registration, are not eligible, except for stable sensory neuropathy (=\< grade 2) and alopecia
• Patients who have received radiotherapy =\< 4 weeks prior to registration, with the exception of palliative radiotherapy, who have not recovered from side effects of such therapy to baseline or grade =\< 1 are not eligible for participation
• Patients with central nervous system (CNS) involvement may participate if they meet all the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment,
• Clinically stable with respect to the CNS tumor at the time of screening
• Patients who have undergone major surgery =\< 4 weeks prior to registration or have not recovered from side effects of such procedure are not eligible for participation
• Patients may not be receiving any other investigational agents
• Patients who have a history of allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab and/or humanized antibodies are not eligible
• Known hypersensitivity to capecitabine, fluorouracil, or any component of the formulation
• Note: prior capecitabine is permitted
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis
• Patients with history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study

Sponsors & Collaborators

• Northwestern University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Related Publications (1)

• Shah AN, Flaum L, Helenowski I, Santa-Maria CA, Jain S, Rademaker A, Nelson V, Tsarwhas D, Cristofanilli M, Gradishar W. Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer. J Immunother Cancer. 2020 Feb;8(1):e000173. doi: 10.1136/jitc-2019-000173.

  PMID: 32060053 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Capecitabine; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: William John Gradishar, MD, FACP, FASCO
• Organization: Northwestern University, Feinberg School of Medicine

w-gradishar@northwestern.edu

(312) 695-4541

Study Officials

• Sarika Jain, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 7, 2017
• Study Start: May 25, 2017
• Primary Completion: April 24, 2019
• Study Completion: May 1, 2021
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-06

Locations

US (2)