AzTrials
AzTrials

Estrogen Receptor NegativePhase 2NCT03044730

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

A Phase 2 study testing Capecitabine, Laboratory Biomarker Analysis and Pembrolizumab in people with Estrogen Receptor Negative and HER2/Neu Negative, run by Northwestern University at 2 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capecitabine, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
25 May 2017to May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 26Show fewer
  • 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
  • Females of child-bearing potential (FOCBP) must have a negative serum or urine pregnancy test within 7 days prior to registration and must be at least within 3 days prior to first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • (Note: a FOCBP is any woman [regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice] who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • Female subjects of childbearing potential (FOCBP) must be willing to use an adequate method of contraception; contraception must be used for the course of the study through 120 days after the last dose of study medication
  • Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Male subjects of childbearing potential must agree to use an adequate method of contraception; contraception must be used starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
  • Patients must be willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Patient must be able to swallow and retain oral medication

Who cannot join

  • 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:
Show all 35Show fewer
  • 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
  • Patients with controlled type I diabetes mellitus on a stable dose of insulin regimen for more than a month may be eligible for this study
  • Patients who have evidence of active, noninfectious pneumonitis or have a history of severe pneumonitis that required treatment with steroids are not eligible for this study; (Note: replacement physiologic dose of steroids [prednisone 10 mg daily or equivalent] are allowed)
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Hypertension that is not controlled on medication (defined as >= 140/100 at rest, average of 3 consecutive readings)
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Clinically significant electrocardiogram (ECG) abnormality, e.g., a repeated demonstration of a QTc interval > 500 ms
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Known positive test for human immunodeficiency virus (HIV)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Active tuberculosis
  • Prior allogeneic bone marrow transplantation or solid organ transplant
  • Administration of a live, attenuated vaccine within 4 weeks before starting the study treatment or anticipation that a live attenuated vaccine will be required during the study
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing (lactating) are not eligible
  • Patients exhibiting any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures are not eligible for participation; this might include, but is not limited to, infection/inflammation, intestinal obstruction, and/or social/psychological complications
  • Patients with impaired gastrointestinal (GI) function or GI disease that may significantly alter absorption of oral capecitabine (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) are not eligible for participation
  • Patients with a history of another malignancy that progressed or required treatment within 5 years prior to registration are not eligible for participation; Note: the exceptions to this include non-melanoma skin cancer or excised carcinoma in situ of the cervix

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Northwestern Lake Forest Hospital

    Lake Forest, Illinois, 60045

Other trials in United States

About this study

Official title: Phase II Study of Pembrolizumab and Capecitabine for Advanced Triple Negative and Hormone-Refractory Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Capecitabine, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03044730
Study groupRoleWhat they receive
Treatment (pembrolizumab, capecitabine)ExperimentalPatients 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.
Receives: Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Approximately 20 months

Secondary outcomes (2)

  1. 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.

    Measured: Up to 9 Cycles (1 cycle = 21 days)

  2. 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).

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2017 (estimated)
  2. Study start25 May 2017
  3. Primary completion24 Apr 2019
  4. Study completionMay 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03044730
Sponsor's protocol ID
NU 16B08
Other IDs
STU00203215, NU 16B08, P30CA060553, NCI-2017-00152
Status last verified
Jun 2020
First submitted
3 Feb 2017
Last updated
13 Jul 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32060053

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Capecitabine, Laboratory Biomarker Analysis and Pembrolizumab in people with Estrogen Receptor Negative and HER2/Neu Negative, run by Northwestern University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median PFS (Median Progression-Free Survival) (time frame: Approximately 20 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03044730, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in