Trastuzumab and Pertuzumab in Treating Patients With Unresectable Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Trastuzumab

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00301899
First received: March 9, 2006
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as trastuzumab and pertuzumab, 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. Giving trastuzumab together with pertuzumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving trastuzumab together with pertuzumab works in treating patients with unresectable locally advanced or metastatic breast cancer that did not respond to previous trastuzumab.


Condition Intervention Phase
Breast Cancer
Biological: pertuzumab
Biological: trastuzumab
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Efficacy and Safety Using Combined Monoclonal Antibodies, Trastuzumab and Pertuzumab in Subjects With Her-2 Overexpressed Locally Advanced and Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Minimal rate of clinical responses [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Time to response [ Designated as safety issue: No ]
  • Response duration [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: December 2005
Study Completion Date: October 2007
Detailed Description:

OBJECTIVES:

Primary

  • Determine the objective response rate in patients with HER2/neu-overexpressing, inoperable locally advanced or metastatic breast cancer refractory to trastuzumab (Herceptin®)-based therapy treated with trastuzumab and pertuzumab.
  • Determine the safety and tolerability of this regimen in these patients.

Secondary

  • Determine the time to progression, progression-free survival, duration of response, and the percentage of patients free from disease progression at 3, 6, and 12 months.
  • Correlate pre-treatment HER-2/neu phosphorylation and the phosphorylation of downstream markers of signaling pathways using tumor tissue and blood with pertuzumab sensitivity and/or trastuzumab resistance in these patients.

OUTLINE: This is an open-label study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1 and pertuzumab IV over 30-60 minutes on day 2 of course 1. Beginning in course 2 and for all subsequent courses, patients receive both trastuzumab and pertuzumab on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer of 1 of the following stages:

    • Metastatic disease (stage IV)
    • Inoperable locally advanced disease

      • Disease progression after prior neoadjuvant chemotherapy required
  • Disease progression on or after trastuzumab (Herceptin®) based-therapy

    • Received 1-3 prior trastuzumab-based regimens
  • HER2/neu-positive tumor, defined as 3+ by fluorescent in situ hybridization
  • Measurable disease, defined as at least 1 lesion that can be measured in at least one dimension
  • No clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT scan or MRI

    • Brain and/or leptomeningeal metastases allowed if patient has stable lesions after standard treatment (surgery or radiotherapy), is asymptomatic on neurological exam, and is not receiving corticosteroid therapy to control symptoms
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Male or female
  • Menopausal status not specified
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Alkaline phosphatase < 5 times ULN
  • AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • LVEF above lower limit of normal by echocardiogram or MRI
  • No clinical signs or symptoms of heart failure
  • No uncontrolled hypertension (i.e., blood pressure ≥ 180/100 mm Hg)
  • No significant valvular disease (i.e., aortic or mitral regurgitation of 3 or 4+/4+ severity or stenosis of either valve)
  • No history of uncontrolled cardiac arrhythmia
  • No symptomatic or asymptomatic myocardial infarction
  • No angina pectoris requiring medication
  • No other documented significant cardiac event
  • No poorly controlled diabetes mellitus (i.e., fasting blood sugar ≥ 200 mg/dL)
  • No history of hypersensitivity reaction to trastuzumab
  • No AIDS
  • No nonmalignant condition requiring ≥ 20 mg of prednisone (or equivalent)
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No ongoing liver disease, including viral or other hepatitis, alcohol abuse, or cirrhosis
  • No other serious medical illness
  • No medical or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • More than 3 weeks since prior investigational anticancer agents
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), major surgery, or immunotherapy
  • More than 4 weeks since prior radiotherapy except short-course palliative radiotherapy for bone pain
  • More than 2 weeks since prior and no concurrent oral hormonal therapy
  • More than 4 weeks since prior fulvestrant
  • No prior doxorubicin hydrochloride or doxorubicin HCl liposome at a cumulative dose of > 360 mg/m^2
  • No prior mitoxantrone hydrochloride at a cumulative dose of > 120 mg/m^2
  • No prior epirubicin hydrochloride at a cumulative dose of > 600 mg/m^2
  • No prior idarubicin at a cumulative dose of > 90 mg/m^2
  • No concurrent radiation therapy, including for symptomatic bone metastases
  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: NCT00301899

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Chia Portera, MD NCI - Medical Oncology Branch
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00301899     History of Changes
Obsolete Identifiers: NCT00263224
Other Study ID Numbers: 060035, 06-C-0035, NCI-P6660, CDR0000462639
Study First Received: March 9, 2006
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
recurrent breast cancer
male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Pertuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014