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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00238290
First received: October 12, 2005
Last updated: June 4, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab + Letrozole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Objective response rate as assessed by CT scan or MRI every 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to tumor progression (TTP) every 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Overall survival every 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Toxicity every 3 months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: May 2005
Study Completion Date: April 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
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.
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.

Detailed 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.

  Eligibility

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

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
  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: NCT00238290

Locations
Switzerland
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Saint Claraspital AG
Basel, Switzerland, CH-4016
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Liestal
Liestal, Switzerland, CH-4410
Ospedale Beata Vergine
Mendrisio, Switzerland, CH-6850
Praxis Dr. Beretta
Rheinfelden, Switzerland, CH-4310
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
City Hospital Triemli
Zurich, Switzerland, CH-8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Dieter Koeberle, MD Cantonal Hospital of St. Gallen
  More Information

Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00238290     History of Changes
Other Study ID Numbers: SAKK 23/03, EU-20527
Study First Received: October 12, 2005
Last Updated: June 4, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
recurrent 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
Letrozole
Trastuzumab
Aromatase Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014