Clinical Trials /

Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

NCT01730833

Description:

This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation work in treating patients with human epidermal growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies, such as pertuzumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

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Title

  • Brief Title: Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With alteration'>HER2-Positive Advanced Breast Cancer
  • Official Title: Phase II Prospective Open Label Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 12147
  • SECONDARY ID: NCI-2012-02371
  • SECONDARY ID: R01CA166020
  • SECONDARY ID: AACR Grant 12-60-26-WANG
  • NCT ID: NCT01730833

Conditions

  • alteration'>HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Adenocarcinoma
  • Inflammatory Breast Carcinoma

Interventions

DrugSynonymsArms
pertuzumab2C4 antibody, monoclonal antibody 2C4, Perjeta, rhuMAb-2C4Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
trastuzumabanti-c-erB-2, Herceptin, MOAB HER2Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
paclitaxel albumin-stabilized nanoparticle formulationABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxelTreatment (pertuzumab, trastuzumab, nab-paclitaxel)

Purpose

This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation work in treating patients with human epidermal growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies, such as pertuzumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine efficacy of administration of pertuzumab in combination with trastuzumab with
      nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in subjects with
      stage IV human epidermal growth factor receptor (HER)-2 overexpressing metastatic breast
      cancer (MBC) as measured by progression free survival (PFS).

      II. To determine the efficacy as neoadjuvant treatment of the regimen in alteration'>HER2+ locally
      advanced breast cancer (LABC) as defined by pathologic complete response (pCR).

      SECONDARY OBJECTIVES:

      I. To evaluate the safety of pertuzumab when added to trastuzumab and nab-paclitaxel in HER-2
      overexpressing MBC and LABC cancer as assessed by the frequency and severity of adverse
      events (AEs), abnormal findings on physical examination, laboratory tests, and vital signs.

      II. To evaluate the objective response rate (Response Evaluation Criteria in Solid Tumors
      [RECIST] 1.1) and duration of response in MBC.

      III. To evaluate the efficacy of the regimen by assessing tumor response including assessment
      of residual cancer burden (RCB) scores in LABC.

      IV. To assess the progression free survival (MBC), relapse-free survival (LABC) and overall
      survival in all patients.

      V. To perform exploratory circulatory gene, micro-ribonucleic acid (RNA), and exosome
      profiling as well as protein and glycomic profiling.

      VI. To assess the feasibility of molecular profiling in both primary and metastatic tumor
      samples.

      VII. To assess numerical and qualitative aspects of circulating tumor cells and circulating
      tumor-derived deoxyribonucleic acid (DNA).

      OUTLINE: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on day 1,
      trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation
      IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of
      disease progression or unacceptable toxicity (patients with MBC) or for 6 courses in the
      absence of disease progression or unacceptable toxicity (patients with LABC).

      After completion of study treatment, patients are followed up every 3 months for 4 years and
      then every 6 months for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pertuzumab, trastuzumab, nab-paclitaxel)ExperimentalPatients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • paclitaxel albumin-stabilized nanoparticle formulation

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be diagnosed with metastatic cytologically or histologically confirmed
             adenocarcinoma of the breast with HER2 over-expression or with newly diagnosed locally
             advanced (including inflammatory) breast cancer (LABC) with stage II-III disease;
             patients with metastatic (stage IV) disease (MBC) must have measurable lesions

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control or abstinence) prior to study entry and
             for six months following duration of study participation; should a woman become
             pregnant or suspect that she is pregnant while participating on the trial, she should
             inform her treating physician immediately

          -  Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and
             overexpressing HER2 by immunohistochemistry (IHC) (3+), or, alteration'>HER2-amplified by
             fluorescence in situ hybridization (FISH) or by alternative gene testing

          -  For patients with LABC, no prior therapy is allowed

          -  For patients with MBC, prior adjuvant chemotherapy and trastuzumab more than or equal
             to 12 months prior to enrollment are allowed

          -  No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer

          -  Left ventricular ejection fraction (LVEF) >= 50% (determined by echocardiogram or
             multigated acquisition scan) within 42 days of treatment

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Hemoglobin >= 9 g/dl

          -  Leukocytes >= 3.0 x 10^9/L

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin =< 1.3 mg/dl (institutional upper limit of normal)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2 x institutional upper limit of normal

          -  Creatinine within normal institutional limits or creatinine clearance > 50 mL/min/1.73
             m^2 for patients with creatinine levels above institutional normal (using
             Cockcroft-Gault formula)

          -  All radiology studies (study requiring staging) must be performed within 35 days prior
             to the start of therapy

          -  No serious medical conditions such as myocardial infarction within 6 months prior to
             entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled
             hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders,
             serious infections, active peptic ulcer disease, psychiatric illness, or any other
             medical conditions that might be aggravated by treatment or limit compliance

          -  Currently, no active second malignancy other than non-melanoma skin cancer; note:
             patients are not considered to have a "current active" malignancy if they have
             completed anti-cancer therapy and are considered by their physicians to have a less
             than 30% chance of relapse

          -  All patients must have the ability to understand and the willingness to sign an
             informed consent

          -  Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at
             screening for patients of child-bearing potential

          -  No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of
             the newly diagnosed metastatic breast cancer; patients are allowed to have had prior
             chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to
             enrollment into this study; patients with a prior diagnosis of malignancy treated >= 5
             years ago are eligible, provided that they have not received prior nab-paclitaxel as
             part of their prior treatment regimen, and that they meet all eligibility criteria

        Exclusion Criteria:

          -  Known active hepatitis B or C

          -  Known active human immunodeficiency virus (HIV)

          -  Prior breast cancer or other invasive malignancy treated within 5 years

          -  Pregnancy

          -  Neuropathy > grade 1

          -  Any other intercurrent medical/psychological problem deemed exclusionary by the
             treating physician or investigators/principal investigator (PI)

          -  Cumulative dose of doxorubicin or equivalent of > 360 mg/m^2 during prior adjuvant
             therapy

          -  LVEF < 50% during previous trastuzumab therapy

          -  Central nervous system metastases

          -  Another malignancy excluding basal cell skin cancer

          -  Pregnant women

          -  Subjects will be excluded who, in the opinion of the investigator, may not be able to
             comply with the safety monitoring requirements of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:Time from initiation of treatment until objective disease progression, assessed up to 5 years
Safety Issue:
Description:Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From the initial date of treatment to the recorded date of death, assessed up to 5 years
Safety Issue:
Description:Estimated by the Kaplan-Meier method. Corresponding survival times with 90% confidence limits will be determined.
Measure:Number of patients experiencing serious adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame:Up to 30 days post-treatment
Safety Issue:
Description:Characterized by type of AE and grade, and by the time of onset in relation to the first day of therapy for each course. Attribution to SAEs to treatment (unrelated, unlikely, possible, probable, or definite) will also be reported. The cumulative percentage of patients experiencing treatment related SAEs and its relationship to treatment duration will be reported.
Measure:Objective response rate (RECIST 1.1) (MBC patients)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Clinical benefit rate, defined as the rate of complete response (CR) plus partial response (PR) plus stable disease (SD) (MBC patients)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Complete pathologic response, analyzed using residual cancer burden score (LABC patients)
Time Frame:Up to 18 weeks (time of definitive surgery)
Safety Issue:
Description:
Measure:Relapse-free survival (LABC patients)
Time Frame:Up to 5 years
Safety Issue:
Description:Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

June 12, 2017

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