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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 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: October 29, 2014
Last verified: October 2014
  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.


Condition Intervention Phase
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
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. The corresponding median survival time (with 90% confidence limits) will be determined.

  • PFS (MBC patients) [ 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. The corresponding median survival time (with 90% confidence limits) will be determined.

  • PFS (LABC patients) [ 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. The corresponding median survival time (with 90% confidence limits) will be determined.


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.

  • Objective response rate (RECIST 1.1) (MBC patients) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Complete pathologic response, analyzed using residual cancer burden score (LABC patients) [ Time Frame: Up to 18 weeks (time of definitive surgery) ] [ Designated as safety issue: No ]
  • Relapse-free survival (LABC patients) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.


Estimated Enrollment: 50
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 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 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.

  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 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, 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Antelope Valley Recruiting
Lancaster, California, United States, 93534
Contact: Nimit Sudan, MD    877-828-3627    nsudan@coh.org   
Principal Investigator: Nimit Sudan, MD         
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: October 29, 2014
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on October 29, 2014