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

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

  • ORG STUDY ID: CBYL719XUS06T
  • NCT ID: NCT02379247

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
BYL719PI3K inhibitorBYL719 Dose Expansion
Nab-paclitaxelTaxaneBYL719 Dose Expansion

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 each year 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 1 will be completed before Part 2 begins.

      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

NameTypeDescriptionInterventions
Co-hort 1 BYL719 (250mg)+Nab-paclitaxelExperimentalBYL719: 250mg daily on day 1-28 Nab-paclitaxel: 100mg/m2 IV days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)
  • BYL719
  • Nab-paclitaxel
Co-hort 2 BYL719 (300mg)+Nab-paclitaxelExperimentalBYL719: 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 (Window for Nab-paclitaxel is +/- 1 day)
  • BYL719
  • Nab-paclitaxel
Co-hort 3 BYL719 (350mg)+Nab-paclitaxelExperimentalBYL719: 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 (Window for Nab-paclitaxel is +/- 1 day)
  • BYL719
  • Nab-paclitaxel
BYL719 Dose ExpansionExperimentalBYL719: 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 (Window for Nab-paclitaxel is +/- 1 day)
  • 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. NOTE: For subjects who are, or who have previously
             received, endocrine therapy for breast cancer, the treating investigator will decide
             how many days should pass between the last dose of endocrine therapy and the first
             dose of study treatment.

          -  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

        NOTE: Subjects who have had previous treatment with Nab-Paclitaxel will NOT be excluded if
        given in the adjuvant or neoadjuvant setting Only in the metastatic setting, will subjects
        previously treated with Nab-Paclitaxel be excluded from this trial.

          -  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 NOTE: Subjects who have had previous
             treatment with Nab-Paclitaxel will NOT be excluded if given in the adjuvant or
             neoadjuvant setting.

        NOTE: Only in the metastatic setting, will subjects previously treated with Nab-Paclitaxel
        be excluded from this trial.

          -  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 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

          -  Patient has received previous treatment with a PI3K inhibitor. Exceptions may be made
             for subjects who discontinued treatment with a previous PI3K inhibitor for reasons
             other than toxicity or progression and as long as it has been > 12 months since
             discontinuation of the previous PI3K inhibitor. This exception will require prior
             approval from the study PI.

          -  Subjects having participated in a clinical trial within 30 days prior enrollment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Recommended Phase II Dose of BYL719 + Nab-paclitaxel to be used in combination to treat advanced HER-2 negative breast cancer
Time Frame:12 months
Safety Issue:
Description:Phase I Dose escalation

Secondary Outcome Measures

Measure: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
Time Frame:24 months
Safety Issue:
Description:Determine Clinical Benefit Rate
Measure:Pharmacokinetics - Nab paclitaxel plasma concentration vs time profile when given with BYL
Time Frame:12 months
Safety Issue:
Description:Determination of pharmacokinetics of BYL719 when combined with Nab-paclitaxel
Measure:Pharmacokinetics - BYL plasma concentration vs time profile when given with Nab paclitaxel
Time Frame:12 months
Safety Issue:
Description:Determination of pharmacokinetics of Nab-paclitaxel when combined with BYL719
Measure:Progression-Free Survival and Overall Survival
Time Frame:36 months
Safety Issue:
Description:Determine progression free survival and overall survival

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Priyanka Sharma

Trial Keywords

  • HER-2 Negative
  • Metastatic Breast Cancer

Last Updated

November 6, 2020