Clinical Trials /

BYL719 and Nab-Paclitaxel in Locally Recurrent or Metastatic HER-2 Negative Breast Cancer

NCT02379247

Description:

Investigate the use of BYL719 as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">BYL719</span> and <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> in Locally Recurrent or Metastatic <span class="go-doc-concept go-doc-biomarker">HER-2</span> Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: BYL719 and Nab-Paclitaxel in Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
  • Official Title: Phase I/II Study of BYL719 and Nab-Paclitaxel in Subjects With Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02379247

    ORG ID: CBYL719XUS06T

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    BYL719 PI3K inhibitor Co-hort 1 BYL719 (250mg)+Nab-paclitaxel, Co-hort 2 BYL719 (300mg)+Nab-paclitaxel, Co-hort 3 BYL719 (350mg)+Nab-paclitaxel, BYL719 Dose Expansion
    Nab-paclitaxel Taxane Co-hort 1 BYL719 (250mg)+Nab-paclitaxel, Co-hort 2 BYL719 (300mg)+Nab-paclitaxel, Co-hort 3 BYL719 (350mg)+Nab-paclitaxel, BYL719 Dose Expansion

    Trial Purpose

    Investigate the use of BYL719 as combination therapy with Nab-Paclitaxel in locally
    recurrent or metastatic HER-2 negative breast cancer.

    Detailed Description

    Breast cancer is the most common cancer and the second leading cause of cancer related death
    in American women. Despite recent improvement in the treatment of breast cancer, 40,000
    women still die in the US as a result of breast cancer. Chemotherapy (usually consisting of
    sequential single agent)remains the backbone of treatment for patients with HER-2 negative
    metastatic breast cancer. A majority of patients show an initial response to treatment, but
    all eventually show disease progression.

    The purpose of this study is to determine the highest dose of BYL719 combined with
    Nab-Paclitaxel that results in no serious side effects. The safety and effectiveness of
    BYL719 combined with Nab-Paclitaxel to treat patients with HER-2 negative breast cancer will
    be assessed, along with the determination of how long this drug combination will keep the
    disease from getting worse.

    The study will be done in two parts:

    Part 1 will determine the highest dose of BYL719 that is safe and tolerable to take in
    combination with Nab-Paclitaxel.

    Part 2 will investigate taking BYL719 (at the dose determined in Part 1) + Nab-Paclitaxel is
    safe and effective for patients with HER-2 negative breast cancer.

    Trial Arms

    Name Type Description Interventions
    Co-hort 1 BYL719 (250mg)+Nab-paclitaxel Experimental BYL719: 250mg daily on day 1-28 Nab-paclitaxel: 100mg/m2 IV days 1, 8, 15 BYL719, Nab-paclitaxel
    Co-hort 2 BYL719 (300mg)+Nab-paclitaxel Experimental BYL719: 300mg by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle BYL719, Nab-paclitaxel
    Co-hort 3 BYL719 (350mg)+Nab-paclitaxel Experimental BYL719: 350mg by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle BYL719, Nab-paclitaxel
    BYL719 Dose Expansion Experimental BYL719: MTD from Phase I by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle BYL719, Nab-paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    - HER-2 negative breast cancer that is either stage III disease not amenable to
    curative therapy or stage IV

    - Have measurable disease of 2 cm by conventional measurement or 1 cm on spiral CT

    - Prior chemotherapy for metastatic disease is allowed. No limitations to number of
    prior chemotherapies. Prior taxanes (except Nab-Paclitaxel) is allowed if it has been
    6 months since prior taxane.

    - All patients should have received at least one line of chemotherapy in either the
    advanced or adjuvant setting and hormonal therapy (where appropriate)

    - ECOG Performance status 2

    - Subject is able to swallow and retain oral medicines

    - Laboratory values as follows:

    - Absolute neutrophil count 1500/uL

    - Platelets 100,000/uL (no transfusion 2 weeks)

    - Hemoglobin > 9 g/dL (may be reached by transfusion)

    - Total bilirubin within normal range or 1.5X IULN if liver metastases

    - Total bilirubin 3.0X IULN with direct bilirubin within normal range in
    subjects with Gilbert's Syndrome

    - AST(SGOT)/ALT(SPGT) 2.5X IULN or 5X IULN if liver metastases

    - Serum creatinine 1.5X IULN

    - INR 1.5

    - Fasting plasma glucose 140 mg/dL or 7.8 mmol/L

    - HBA1c 8%

    - Potassium, calcium (corrected for serum albumin) & magnesium within IULN

    - IV bisphosphate and denosumab for bony metastatic disease will be allowed

    - Radiation to bony metastases is allowed 14 days before starting study treatment

    - Subjects with previously treated brain metastases who are free of CNS symptoms and >
    3 months from treatment are eligible

    - Subjects should be > 2 weeks from last chemotherapy for breast cancer AND be
    recovered to Grade 1 from related side effects

    - Women of child bearing potential and their partners must use contraception prior to
    study entry, continuing for 90 days after treatment

    Exclusion Criteria:

    - Other medical or psychiatric disorder placing the subject at undue risk for treatment
    complications

    - Subject is pregnant or nursing

    - Subject has been treated with Nab-Paclitaxel

    - Subject has inflammatory breast cancer

    - Subject has a known hypersensitivity to Nab-Paclitaxel or BYL719

    - Subject has a concurrent malignancy or malignancy within 3 years, except for
    basal/squamous cell carcinoma, non-melanoma skin cancer or curatively resected
    cervical cancer

    - Subject has diabetes mellitus or steroid-induced diabetes mellitus

    - Subject has impaired gastrointestinal function or disease altering the absorption of
    study drugs

    - Subject is classified into Child-Pugh class C

    - Subject has a known history of HIV infection (testing not mandatory)

    - Subject has an active and uncontrolled infection

    - Subject has symptomatic/untreated CNS disease

    - Subject has Grade 2 peripheral neuropathy

    - Subject has a medically documented history of, or active mental illness. Dose and
    schedule for any psychotropic treatment must be stabile for the 6 weeks before
    starting study drug.

    - Subject has Grade 3 anxiety

    - Subject has active or history of cardiac disease including:

    - Unstable angina within 6 months before study entry

    - Symptomatic peritonitis

    - Documented heart attack within 6 months before study entry

    - History of congestive heart failure (New York Heart Association functional
    classification III-IV)

    - Documented cardiomyopathy

    - Left Ventricular Ejection Fraction (LVEF) < 50% measured by Multiple Gated
    Acquisition (MUGA) scan or echocardiogram (ECHO)

    - Subject has any of the following cardiac abnormalities

    - Ventricular arrhythmias except benign premature contractions

    - Other arrhythmias requiring a pacemaker or not controlled with medicine

    - Conduction abnormality requiring a pacemaker

    - Subject has a QTcF > 480 msec on the screening ECG

    - Subject must continue to take a drug that causes ECG abnormalities or induces
    Torsades de Pointes

    - Subject had major surgery within 14 days before starting study drug or has not
    recovered from major side effects

    - Subject is taking or has taken systemic corticosteroids 2 weeks prior to starting
    study drug or have not fully recovered from side effects

    - Subject is taking drugs known to be inhibitors or inducers of CYP3A.

    - Subject is taking warfarin or other coumarin-derived anti-coagulant. Therapy with
    heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed

    - Subjects having participated in a clinical trial within 30 days prior enrollment

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Phase I: Recommended Phase II Dose of BYL719 + Nab-paclitaxel to be used in combination to treat advanced HER-2 negative breast cancer

    Phase II: Overall Response Rate of subjects treated at the recommended phase II dose

    Secondary Outcome Measures

    Clinical Benefit Rate at 16 weeks of study treatment based on subjects having complete response, partial response or stabile disease at the recommended phase II dose

    Pharmacokinetics - Nab paclitaxel plasma concentration vs time profile when given with BYL

    Pharmacokinetics - BYL plasma concentration vs time profile when given with Nab paclitaxel

    Progression-Free Survival and Overall Survival

    Trial Keywords

    HER-2 Negative

    Metastatic Breast Cancer