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

This study is currently recruiting participants.
Verified January 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01730833
First received: November 16, 2012
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

This phase II trial studies how well giving pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation together works in treating patients with human epidermal growth factor receptor (HER)2-positive metastatic 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


Condition Intervention Phase
HER2-positive Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Biological: pertuzumab
Biological: trastuzumab
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Prospective Open Label Single Arm Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Time from initiation of treatment until objective disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier method.

  • Response rate (complete response [CR] + partial response [PR]) based on the RECIST version 1.1 [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Estimated with 95% confidence intervals.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: From the initial date of treatment to the recorded date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier method. Corresponding survival times with 90% confidence limits will be determined.

  • 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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 45
Study Start Date: July 2013
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients 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.
Biological: pertuzumab
Given IV
Other Names:
  • 2C4 antibody
  • monoclonal antibody 2C4
  • Perjeta
  • rhuMAb-2C4
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Names:
  • ABI-007
  • nab paclitaxel
  • nab-paclitaxel
  • nanoparticle albumin-bound paclitaxel
Other: laboratory biomarker analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To evaluate the safety of pertuzumab when added to trastuzumab and abraxane (paclitaxel albumin-stabilized nanoparticle formulation) in stage IV HER-2 overexpressing breast cancer 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 and duration of response.

III. To evaluate the objective tumor response (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 criteria) where possible.

IV. To assess the overall survival.

V. To perform exploratory protein and glycomic biomarker profiling.

VI. To perform exploratory micro ribonucleic acid (RNA) and exosome profiling.

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. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be diagnosed with metastatic cytologically or histologically confirmed adenocarcinoma of the breast with HER2 over-expression; patients must have measurable and/or evaluable 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), or, in case of IHC of 2, positive by fluorescence in situ hybridization (FISH) >= 2 or by alternative gene testing
  • Prior adjuvant chemotherapy and trastuzumab more than or equal to 6 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
  • Prior radiotherapy is allowed provided that there is documentation of progression (either locally or systemically)
  • Patients may have had prior chemotherapy in the adjuvant setting
  • Toxic effects from prior therapy must have resolved to grade 1 or less except for peripheral neuropathy and alopecia
  • Hemoglobin >= 90 g/dl - Leukocytes >= 3.0 x 10^9/L
  • Absolute neutrophil count (ANC) >= 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 (=< 5 times the upper limit of normal [ULN] for patients with liver metastases)
  • 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 must be performed =< 4 weeks 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 6 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 (due to the potential for disease treatment-related pharmacological and liver function-specific interactions)
  • Known active human immunodeficiency virus (HIV) (due to the complexity and potential pharmacological interactions between the standard neoadjuvant therapeutic agents, and highly active antiretroviral therapy [HAART])
  • 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)
  • Recurrence < 6 months since completion of adjuvant treatment
  • Prior chemotherapy or trastuzumab treatment for metastatic disease
  • 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
  • Hemoglobin < 9 g/dL
  • ANC < 1500/mcL
  • Platelet < 100,000/mcL
  • Creatinine clearance =< 50 mL/min as measured by either the Cockcroft-Gault method or 24-hour creatinine clearance)
  • AST (SGOT)/ALT (SGPT) > 2 x institutional upper limit of normal
  • Uncontrolled hypertension or unstable angina, congestive heart failure (New York Heart Association classification), or myocardial infarction within 6 months of enrollment
  • Pregnant women
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01730833

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: George Somlo, MD    800-826-4673    gsomlo@coh.org   
Principal Investigator: George Somlo         
City of Hope- South Pasadena Cancer Center Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler, MD    800-826-4673    skoehler@coh.org   
Principal Investigator: Stephen C. Koehler         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: George Somlo, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01730833     History of Changes
Other Study ID Numbers: 12147, NCI-2012-02371, R01CA166020, AACR Grant 12-60-26-WANG
Study First Received: November 16, 2012
Last Updated: January 21, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Paclitaxel
Trastuzumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014