Clinical Trials /

Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients

NCT01802970

Description:

To determine the safety of administering anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in patients with metastatic breast cancer (MBC), as well as determining blood immune cell transcriptional signatures in patients who undergo IL-1 receptor blockade.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Safety and Blood Immune Cell Study of <span class="go-doc-concept go-doc-intervention">Anakinra</span> Plus Physician's <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> Choice in Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Patients

Title

  • Brief Title: Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients
  • Official Title: Pilot Safety and Blood Immune Cell Transcriptional Profiling Study of Anakinra Plus the Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients
  • Clinical Trial IDs

    NCT ID: NCT01802970

    ORG ID: 012-099

    Trial Conditions

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Anakinra plus Standard of Care Anakinra: kineret, Nab paclitaxel: Abraxane, Capecitabine: Xeloda, Eribulin: Halaven, Vinorelbine: Navelbine Anakinra plus Standard of Care

    Trial Purpose

    To determine the safety of administering anakinra plus the physician's chemotherapy choice
    (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in patients with metastatic
    breast cancer (MBC), as well as determining blood immune cell transcriptional signatures in
    patients who undergo IL-1 receptor blockade.

    Detailed Description

    In an attempt to reverse the immune suppressive microenvironment and to enhance chemotherapy
    effectiveness, decrease tumor metagenicity and decrease IL-1-induced fatigue, metastatic
    breast cancer (MBC) patients will be treated with chemotherapy plus anakinra. This is a
    pilot safety, single arm, open label trial. The objective is to determine the safety of
    anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine,
    eribulin, or vinorelbine in patients with MBC and to define an anakinra-induced anti-IL-1
    whole blood transcriptional profile.

    Trial Arms

    Name Type Description Interventions
    Anakinra plus Standard of Care Experimental Patients will undergo a 2-week run-in treatment of daily anakinra alone. This will be followed by daily anakinra (100 mg SC) plus the physician's chemotherapy ( TPC) choice of standard of care (SOC) for a maximum of 6 months.TPC choice includes nab paclitaxel (100 mg/m^2 Intravenous on day 1,8 &15 of a 28 day cycle), or capecitabine (1000mg/m^2 per oral; BID choice: 14 days on, 7 days off OR 7 days on, 7 days off of a 21 day cycle), or eribulin (1.4 mg/m^2 intravenous on day 1 & 8 of a 21 day cycle), or vinorelbine (25mg/m^2 on day 1,8,15 of a 28 day cycle). After 6 months, patients may continue their SOC treatment alone until disease progression or intolerable toxicity. Anakinra plus Standard of Care

    Eligibility Criteria

    Inclusion Criteria:

    - Female or male patients 18 years of age.

    - Histologically confirmed invasive breast cancer, locally unresectable or metastatic.

    - No more than 4 prior chemotherapy regimens for metastatic disease.

    - Patients currently being treated with nab paclitaxel, capecitabine,eribulin, or
    vinorelbine who have had a CR, PR, or SD and who have developed Grade 2, 3, or 4
    fatigue on the chemotherapy are eligible for the study. It should be anticipated that
    these patients will continue to be treated on the same chemotherapy agent for at
    least 3 more months beyond the time of enrollment.

    - Prior hormonal therapy in the adjuvant or metastatic setting is permitted.

    - HER2-negative breast cancer. If HER2-, it is defined as follows:

    1. FISH-negative (FISH ratio <2.0), or

    2. IHC 0-1+, or

    3. IHC 2+ AND FISH-negative (FISH ratio<2.0)

    - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

    - Adequate hematologic function, defined by:

    1. Absolute neutrophil count (ANC) >1500/mm^3

    2. Platelet count 100,000/mm^3

    3. Hemoglobin >8 g/dL

    - Adequate liver function, defined by:

    1. AST and ALT 2.5 x the upper limit of normal (ULN) or 5 x ULN in presence of
    liver metastases

    2. Total bilirubin 1.5 x ULN

    - Adequate renal function, defined by:

    a. Serum creatinine 1.5 x ULN or calculated creatinine clearance of 40 ml/min

    - Measurable or nonmeasurable disease by RECIST v1.1 criteria

    - Life expectancy 24 weeks

    - Adequate recovery from recent surgery

    1. Major surgical procedure >28 days from study entry

    2. Minor surgical procedure >7 days from study entry (Portacath placement accepted
    - patients can start treatment <7 days after portacath placement.)

    - Patients with previous history of invasive cancers (including breast cancer) are
    eligible if definitive treatment was completed more than 5 years prior to initiating
    current study treatment, and there is no evidence of recurrent disease.

    - Patient must be accessible for treatment and follow-up.

    - All patients must be able to understand the investigational nature of the study and
    give written informed consent prior to study entry

    Exclusion Criteria:

    - Patients with active or untreated brain metastases or meningeal metastases are
    ineligible. Patients who have had brain metastases resected, or have received brain
    radiation therapy >4 weeks prior to study entry are eligible if they meet all of the
    following criteria: 1) patient has been off dexamethasone for >2 weeks; 2) no known
    progression of brain metastasis.

    - Previous radiotherapy for metastatic disease completed <2 weeks prior to study
    treatment initiation.

    - Women who are pregnant or lactating. All patients with reproductive potential must
    agree to use effective contraception from time of study entry until at least 3 months
    after the last administration of study drug.

    - Patients who have any severe and/or uncontrolled medical conditions or other
    conditions that could affect their participation such as: -

    1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
    the normal predicted value and/or O2 saturation that is 88% or less at rest on
    room air

    2. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

    3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
    C).

    - History of any other disease, physical examination finding, or clinical laboratory
    finding giving reasonable suspicion of a disease or condition that contraindicates
    use of an investigational drug, or that might affect interpretation of the results of
    this study, or render the subject at high risk for treatment complications.

    - Patients may not receive any other investigational treatments while participating in
    this study.

    - Patients receiving chronic, systemic treatment with corticosteroids or another
    immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

    - Concurrent severe, uncontrolled infection or intercurrent illness including, but not
    limited to, ongoing or active infection, or psychiatric illness/social situations
    that would limit compliance with study requirements.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 80 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Safety - Adverse Events in participants

    Secondary Outcome Measures

    To determine investigator-assessed objective response rate, clinical benefit rate, progression-free survival, and rates of chemotherapy or cancer-related anemia (HgB<10), and an anakinra-induced anti-IL-1 blood transcriptional signatures

    Trial Keywords

    Anakinra

    Nab Paclitaxel

    Capecitabine

    Eribulin

    Vinorelbin