Clinical Trials /

2nd Line Treatment With Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer

NCT02624700

Description:

This phase 2 clinical trial will evaluate the efficacy of the combination of pemetrexed and sorafenib in patients with recurrent or metastatic Triple Negative Breast Cancer (TNBC). Candidate pharmacodynamic and predictive biomarkers will also be evaluated.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of Pemetrexed and Sorafenib for Recurrent or Metastatic <span class="go-doc-concept go-doc-keyword">Triple Negative</span> Breast Cancer

Title

  • Brief Title: Study of Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer
  • Official Title: Phase 2 Study of Pemetrexed and Sorafenib for Treatment of Recurrent or Metastatic Triple Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02624700

    ORG ID: MCC-14-10790

    NCI ID: HM20005967

    Trial Conditions

    Breast Cancer

    Metastatic Breast Cancer

    Recurrent Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Pemetrexed Alimta A: Pemetrexed + Sorafenib
    Sorafenib Nexvar A: Pemetrexed + Sorafenib

    Trial Purpose

    This phase 2 clinical trial will evaluate the efficacy of the combination of pemetrexed and
    sorafenib in patients with recurrent or metastatic TNBC. Candidate pharmacodynamic and
    predictive biomarkers will also be evaluated.

    Detailed Description

    This study is a single-arm, open-label, phase 2 study of a regimen of dose-dense pemetrexed
    and sorafenib to determine the objective response rate in patients with recurrent or
    metastatic TNBC. Eligible patients will be those who have had disease progression during or
    after treatment for recurrent or metastatic disease with a minimum of 1 previous
    chemotherapy regimen. (There is no maximum number of previous treatment regimens.)
    Correlative studies will be conducted using blood samples and archived tumor samples.

    Simon's two-stage design will be utilized in this study. In the first stage, if there are
    3 patients of the first 18 efficacy-evaluable patients who have a partial or complete
    response, then the trial will end for futility. If 4 patients have a partial or complete
    response, patient accrual will continue in the second stage to add 10 more
    efficacy-evaluable patients.

    The total sample size for the Simon's two-stage design is 35 patients. Based on enrollment
    of 2-3 patients per month, the expected enrollment period will be about 12-18 months.

    Trial Arms

    Name Type Description Interventions
    A: Pemetrexed + Sorafenib Experimental All study participants will get the same study treatment. Each participant will be given pemetrexed intravenously which means by vein (IV) once every 14 days.They will take sorafenib pills by mouth two times each day for 5 days starting on the pemetrexed treatment day. This 14-day schedule is called a treatment cycle. The treatment is Pemetrexed 500mg/m2 IV Day 1 + Sorafenib 400mg PO Days 1-5. Pemetrexed, Sorafenib

    Eligibility Criteria

    Inclusion Criteria

    - Unresectable breast cancer involving chest wall, regional nodes, or distant site

    - Breast cancer determined to be ER-negative and PgR-negative defined for this study as
    < 10% tumor staining by IHC (Note: Eligibility should be based on the ER and PgR
    status reported at the time of the most recent biopsy or resection).

    - Breast cancer determined to be HER2-negative per current American Society of Clinical
    Oncologists/College of American Pathologists (ASCO/CAP) HER2 Guidelines (Note:
    Eligibility should be based on the HER2 status reported at the time of the most
    recent biopsy or resection).

    - Disease progression during or after treatment for recurrent or metastatic disease

    - A minimum of 1 previous chemotherapy regimen for treatment of recurrent or metastatic
    disease

    - Measurable disease per RECIST v1.1

    - Age 18 years

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Ability to swallow oral medications

    - Adequate bone marrow function as defined below:

    - Absolute neutrophil count (ANC) 1,200/mm3

    - Platelet count 100,000/mm3

    - Hemoglobin 9.0 g/dL (untransfused)

    - Adequate renal function as defined below:

    - Calculated creatinine clearance 45 mL/min

    - Adequate hepatic function as defined below:

    - Total bilirubin 1.5 x upper limit of normal (ULN) for the laboratory

    - Aspartate aminotransferase (AST) 3 x ULN for the laboratory, except in the presence
    of known hepatic metastasis, wherein the AST may be 5 x ULN

    - Alanine aminotransferase (ALT) 3 x ULN for the laboratory, except in the presence
    of known hepatic metastasis, wherein the ALT may be 5 x ULN

    - International normalized ratio (INR) 1.5

    - Serum B12 and folate levels lower limit of normal (LLN) for the laboratory (Note:
    Patients may begin B12 and folic acid supplementation and be reconsidered for
    participation in the study when levels are LLN for the laboratory).

    - Ability to take folic acid, vitamin B12, and dexamethasone according to the protocol
    instructions

    - Ability to interrupt chronic non-steroidal anti-inflammatory drugs (NSAIDs) beginning
    2 days before (5 days before for long-acting NSAIDs) and continuing for 2 days
    following administration of pemetrexed

    - Toxicities from previous cancer therapies resolved to grade 1 unless specified
    otherwise in the inclusion or exclusion criteria (Exception: Neuropathy related to
    previous chemotherapy must be resolved to grade 2.)

    - Women who are not postmenopausal or have not undergone hysterectomy must have a
    documented negative serum pregnancy test within 7 days prior to initiating study
    treatment. Note: Postmenopausal is defined as one or more of the following:

    - Age 60 years

    - Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone
    (FSH) and plasma estradiol levels in the postmenopausal range

    - Bilateral oophorectomy

    - A woman of child-bearing potential (WCBP) must agree to use a medically accepted
    method for preventing pregnancy for the duration of study treatment and for 2 months
    following completion of study treatment.

    - Ability to understand and willingness to sign the consent form written in English

    Exclusion Criteria

    - Any investigational agent within 4 weeks prior to initiating study treatment

    - Known or presumed intolerance of pemetrexed or sorafenib

    - Known or suspected malabsorption condition or obstruction

    - Symptomatic or untreated brain metastases (Note: Patients with known brain metastases
    who are asymptomatic and have had post-treatment imaging that indicates stable
    disease in the brain are eligible. Also, note that imaging of the brain is required
    within 8 weeks prior to study registration).

    - Any documented history of clinically identifiable thrombotic, embolic, venous, or
    arterial events such as cerebrovascular accident, transient ischemic attack, deep
    vein thrombosis, or pulmonary embolism within 6 months prior to initiating study
    treatment (Note: Patients with a tumor-associated thrombus of locally-involved
    vessels or with incidental asymptomatic filling defects identified on imaging are not
    excluded).

    - Contraindication to antiangiogenic agents, including:

    - Serious non-healing wound, non-healing ulcer, or bone fracture

    - Major surgical procedure or significant traumatic injury within 4 weeks prior to
    initiating study treatment

    - Pulmonary hemorrhage/bleeding event grade 2 (CTCAE v4.0) within 12 weeks prior to
    initiating study treatment

    - Any other hemorrhage/bleeding event grade 3 (CTCAE v4.0) within 12 weeks prior to
    initiating study treatment

    - Systolic blood pressure (BP) > 160 mmHg or diastolic BP > 100 mmHg despite optimal
    medical management

    - QTcF interval > 450 ms ( grade 1) on electrocardiogram (ECG)

    - If baseline QTcF on screening ECG is grade 1:

    - Check potassium and magnesium serum levels

    - Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm
    exclusion of patient due to QTcF

    - For patients with heart rate < 60 bpm or > 100 bpm, manual read of the QT interval by
    a cardiologist is required, with Fridericia correction applied to determine QTcF
    (Note: If heart rate is 60-100 bpm, manual read of QTcF is not required).

    - Active or clinically significant cardiac disease including any of the following:

    - Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months
    prior to initiating study treatment

    - Myocardial infarction within 6 months prior to initiating study treatment

    - Ventricular arrhythmias requiring anti-arrhythmic therapy other than beta blockers

    - New York Heart Association (NYHA) class III or IV congestive heart failure

    - Serious (ie, grade 3) uncontrolled infection

    - Uncontrolled effusion (Note: Patients with small effusions remaining after
    pleurodesis are eligible. Determination of eligibility based on pleural size will be
    determined by the principal investigator).

    - Known human immunodeficiency virus (HIV) seropositivity (Note: HIV testing is not
    required)

    - Chronic or active hepatitis B or C infection requiring treatment with antiviral
    therapy

    - Seizure disorder requiring enzyme-inducing anti-epileptic drugs (EIAEDs) (Note: If
    the seizure disorder can be managed with agents that are not EIAEDs (eg,
    levetiracetam or valproate), the patient should not be excluded).

    - Planned ongoing administration of a STRONG CYP3A4 inducer (Note: The reference list
    of cytochrome p450 (CYP) isozymes and classification of strong, moderate, and weak
    interactions is available through the FDA website).

    - Pregnancy or breastfeeding

    - Diagnosis or treatment for another malignancy within 3 years of enrollment, with the
    following exceptions: complete resection of basal cell carcinoma or squamous cell
    carcinoma of the skin, any in situ malignancy, and low-risk prostate cancer after
    curative therapy

    - Medical, psychological, or social condition that, in the opinion of the investigator,
    may increase the patient's risk or limit the patient's adherence with study
    requirements

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    The percentage of objective response either Partial Response (PR) or Complete Response(CR).

    Secondary Outcome Measures

    The percentage of progression-free survival (PFS).

    To determine the 2-year survival rate after initial study treatment.

    The amount of reported Adverse events (AEs).

    Trial Keywords

    ER-negative

    PgR-negative

    HER2-negative

    Triple Negative Breast Cancer