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

NCT00238290 | Completed Phase 2 DMC

• 2 other identifiers: SAKK 23/03EU-20527
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 14

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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate as assessed by CT scan or MRI every 3 months

  3 months

Secondary Outcomes (3)

• Time to tumor progression (TTP) every 3 months

  3 months

• Overall survival every 3 months

  3 months

• Toxicity every 3 months

  3 months

Study Arms (1)

Arm A

EXPERIMENTAL

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

Interventions

Trastuzumab + Letrozole DRUG

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.

Arm A

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (14)

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Praxis Dr. Beretta

Rheinfelden, CH-4310, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related 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 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.

  PMID: 21317203 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dieter Koeberle, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2005
• First Posted: October 13, 2005
• Study Start: May 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: April 1, 2011
• Last Updated: May 15, 2019

Record last verified: 2019-05

Locations

CH (14)