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

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00301899

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: pertuzumab Biological: trastuzumab	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Masking:

None (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

Study Start Date :

Dec 1, 2005

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Safety []
Minimal rate of clinical responses []

Secondary Outcome Measures

Time to progression []
Time to response []
Response duration []
Progression-free survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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