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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

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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

- 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

- Hormone receptor status:

- Not specified


- 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 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

- No other serious medical illness

- No medical or psychiatric condition that would preclude study participation


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Chia Portera, MD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Medical Oncology Branch


United States: Food and Drug Administration

Study ID:




Start Date:

December 2005

Completion Date:

October 2007

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • male breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • Breast Neoplasms



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182