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

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ClinicalTrials.gov Identifier: NCT00238290
Recruitment Status : Completed
First Posted : October 13, 2005
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Tracking Information
First Submitted Date  ICMJE October 12, 2005
First Posted Date  ICMJE October 13, 2005
Last Update Posted Date May 15, 2019
Study Start Date  ICMJE May 2005
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2012)
Objective response rate as assessed by CT scan or MRI every 3 months [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00238290 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2012)
  • Time to tumor progression (TTP) every 3 months [ Time Frame: 3 months ]
  • Overall survival every 3 months [ Time Frame: 3 months ]
  • Toxicity every 3 months [ Time Frame: 3 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trastuzumab and Letrozole in Treating Postmenopausal Women With Progressive Advanced Breast Cancer
Official Title  ICMJE 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
Brief 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: 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.
Intervention: Drug: Trastuzumab + Letrozole
Publications * 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 aromatase inhibitor monotherapies in patients with estrogen receptor-positive, HER-2-positive advanced breast cancer: a proof-of-concept trial (SAKK 23/03). Endocr Relat Cancer. 2011 Mar 9;18(2):257-64. doi: 10.1530/ERC-10-0317. Print 2011 Apr.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 4, 2012)
13
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2011
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00238290
Other Study ID Numbers  ICMJE SAKK 23/03
EU-20527
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Swiss Group for Clinical Cancer Research
Study Sponsor  ICMJE Swiss Group for Clinical Cancer Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Dieter Koeberle, MD Cantonal Hospital of St. Gallen
PRS Account Swiss Group for Clinical Cancer Research
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP