Trastuzumab and Letrozole in Treating Postmenopausal Women With Progressive Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

Trastuzumab Monotherapy Followed By the Combination of Trastuzumab and Letrozole in Post-Menopausal Women With ER-Positive, HER-2 Positive Advanced Breast Cancer Resistant to a Nonsteroidal Aromatase Inhibitor: A Multicenter Two-Step Phase II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00238290
• Other study ID #: SAKK 23/03
• Secondary ID: EU-20527
• Status: Completed
• Phase: Phase 2
• Start date: May 2005
• Est. completion date: April 2011

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies, such as 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. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving trastuzumab together with letrozole after disease progression may be an effective treatment for breast cancer.

PURPOSE: This phase II trial is studying how well giving trastuzumab together with letrozole works in treating postmenopausal women with progressive advanced breast cancer.

Description:

OBJECTIVES:

Primary

• Determine the efficacy of trastuzumab (Herceptin®) monotherapy followed by trastuzumab and letrozole in women with progressive advanced breast cancer that is resistant to prior treatment with a nonsteroidal aromatase inhibitor.

Secondary

• Determine the safety profile of this regimen in these patients.

• Correlate HER-2-extracellular domain (ECD) levels with response to treatment in these patients.

• Determine the efficacy of this regimen in these patients.

• Correlate response and time to tumor progression with changes in serum HER-2-ECD levels in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1-3 OR once in week 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression after 9 weeks receive trastuzumab as before and oral letrozole once daily in the absence of further disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 12 weeks until disease progression and then at 6 months.

PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

• Advanced disease

• Measurable disease, defined as = 1 unidimensionally measurable lesion outside previously irradiated areas that is = 20 mm OR = 10 mm if the slice thickness of the CT scan or MRI is = 5 mm

• No nonmeasurable lesions as the only site of measurable disease, including any of the following:

• Osteoblastic bone metastases

• Ascites

• Pleural or pericardial effusions

• Carcinomatous lymphangitis of the lung

• Progressive disease after prior treatment with a nonsteroidal aromatase inhibitor (e.g., letrozole or anastrozole) in an adjuvant or advanced disease setting

• HER-2 amplification = 2 by fluorescence in situ hybridization

• No clinical symptoms or history of CNS or leptomeningeal metastases (no imaging is required)

• No visceral involvement with risk for organ dysfunction

• Hormone receptor status:

• Estrogen receptor- and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Postmenopausal, defined by 1 of the following:

• At least 55 years of age

• Less than 55 years of age with spontaneous cessation of menses for = 1 year

• Less than 55 years of age with spontaneous cessation of menses within the past year, but amenorrheic with biochemical evidence of postmenopausal status

• Underwent prior bilateral oophorectomy

• Radiation or chemically induced menopause (treatment with luteinizing hormone-releasing hormone antagonists must continue during study treatment)

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC = 3,000/mm^3

• Platelet count = 100,000/mm^3

Hepatic

• AST and ALT = 2 times upper limit of normal

Renal

• Creatinine clearance > 30 mL/min

Cardiovascular

• No uncontrolled cardiac disease, including any of the following:

• Unstable angina

• Arrhythmia

• Hypertension

• No history of congestive heart failure

• No myocardial infarction within the past 6 months

• LVEF > 50% by echocardiogram

Pulmonary

• No severe dyspnea at rest

Other

• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer

• No psychiatric disability that would preclude study participation or giving informed consent

• No active autoimmune disease

• No uncontrolled diabetes

• No other serious underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior trastuzumab (Herceptin®)

Chemotherapy

• Prior neoadjuvant or adjuvant chemotherapy allowed

• No prior palliative chemotherapy

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified

Other

• More than 1 month since prior experimental drugs on another clinical trial

• No concurrent drugs that contraindicate study treatment

• No other concurrent anticancer drugs

• No other concurrent investigational drugs

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Trastuzumab + Letrozole
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1-3 OR once in week 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression after 9 weeks receive trastuzumab as before and oral letrozole once daily in the absence of further disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Saint Claraspital AG	Basel
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Bruderholz	Bruderholz
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital Liestal	Liestal
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Praxis Dr. Beretta	Rheinfelden
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	City Hospital Triemli	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Koeberle D, Ruhstaller T, Jost L, Pagani O, Zaman K, von Moos R, Oehlschlegel C, Crowe S, Pilop C, Thuerlimann B; Swiss Group for Clinical Cancer Research (SAKK). Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and arom — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate as assessed by CT scan or MRI every 3 months		3 months
Secondary	Time to tumor progression (TTP) every 3 months		3 months
Secondary	Overall survival every 3 months		3 months
Secondary	Toxicity every 3 months		3 months