Letrozole, Herceptin in Her2neu +, Estrogen Receptor [ER] and/or Progesterone Receptor [PR] Positive, MBC

NCT00134680 | Completed Phase 2

• 2 other identifiers: 11441144-05-6R5
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of the study is to investigate the effects (good and bad) that the combination of the drugs letrozole (also called Femara™) and trastuzumab (also called Herceptin®) has on breast cancer. The United States (US) Food and Drug Administration has approved both letrozole and Herceptin for the treatment of advanced breast cancer. Doctors hope that the combination will work better than either drug alone.

Conditions

Metastatic Breast Cancer

Keywords

estrogen receptor positive; progesterone receptor positive; ErbB2 positive; metastatic breast cancer

Outcome Measures

Primary Outcomes (3)

• To determine the proportion of patients with ER and/or PR positive, ErbB2 positive tamoxifen resistant metastatic breast cancer who achieve complete remission (CR)

• or partial remission (PR)

• or no significant change in lesion size for greater than 24 weeks

Secondary Outcomes (4)

• To determine duration of response and median time to progression with letrozole plus trastuzumab treatment

• To evaluate the clinical adverse experience during treatment with letrozole plus trastuzumab treatment

• To generate a tumor and serum bank from patients receiving combination trastuzumab and letrozole treatment

• To analyze ErbB2 expression on circulating malignant cells during treatment with letrozole and trastuzumab

Study Arms (1)

Letrozole & Trastuzumab

EXPERIMENTAL

Letrozole 2.5 mg tablets daily and Trastuzumab 2 mg/kg by IV weekly

Drug: Letrozole; Drug: Trastuzumab

Interventions

Letrozole DRUG

Letrozole tablets 2.5 mg by mouth daily

Also known as: Femara

Letrozole & Trastuzumab

Trastuzumab DRUG

Weekly trastuzumab (4 mg/kg loading dose given by IV over 90 minutes folowed by 2 mg/kg given by IV weekly over 30 minutes, provided the previous dose was well tolerated.

Also known as: Herceptin

Letrozole & Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Postmenopausal.
• If premenopausal at diagnosis, eligible if undergoes treatment with luteinising hormone-releasing hormone (LHRH) agonist or surgical ovarian ablation before initiating treatment (tx).
• Tumor cell expression of ER and/or PR and ErbB2. Expression can be ascertained on either primary or metastatic site.
• Patient may have received adjuvant and/or neoadjuvant chemotherapy.
• Patient who received adjuvant/neoadjuvant chemotherapy, tx. must have been discontinued for 4 weeks and patient must have recovered from all acute toxicities, except alopecia.
• Prior radiotherapy is permitted as long as it was planned before start of study medication and is completed within 3 weeks of starting trial medication.
• Prior megestrol acetate or raloxifene therapy is permitted, but must be stopped prior to trial entry.
• Prior tamoxifen therapy.
• At least one bidimensionally measurable lesion.
• ECOG performance status 0-2.
• Patient should have life expectancy of 6 months.
• Patient must have adequate hematologic function: absolute neutrophil count (ANC) 1000/mm3; platelets 75,000/mm3.
• Patient must have adequate renal and liver function, defined as: serum creatinine less than or equal to 1.5 times the upper limit of normal; serum bilirubin less than or equal to 1.5 times the upper limit of normal (three times the upper limit of normal for patients with hereditary benign hyperbilirubinaemia); transaminases (ALT, AST) less than or equal to 2.5 times the upper limit of normal in patients without liver metastasis, or less than or equal to 5 times the upper limit of normal in patients with liver metastasis.
• Ejection fractions by multiple-gated acquisition (MUGA) scan or echocardiogram greater than 50%
• Patient must give written informed consent prior to initiation of any invasive study-related procedures that would otherwise not be performed, and must be able to comply with scheduled visits and evaluations.

You may not qualify if:

• Prior exposure to any aromatase inhibitor (aminoglutethimide, formestane anastrozole, letrozole or exemestane) for more than 28 days. Patients that have already started on aromatase inhibitors (AIs) will be eligible for the protocol if they meet all other eligibility requirements and receive loading dose of trastuzumab not more than 28 days after starting AI therapy. Patients who initially received anastrozole or exemestane will be switched to letrozole.
• Prior treatment with trastuzumab
• Prior anthracycline exposure in adjuvant setting \> 360 mg/m2.
• Patients with central nervous system (CNS) involvement with metastatic breast cancer or life threatening lymphangitic or large volume lung or liver disease.
• Patient's only qualifying lesions have been previously irradiated or are scheduled for irradiation following study entry.
• Severe or uncontrolled concomitant disease from other causes.
• More than 1 prior course of chemotherapy for metastatic disease. If patient has received one course of palliative chemotherapy, acute toxicities must have resolved and patient must be experiencing progressive disease at time of enrollment.
• ECOG performance status 3 or 4.
• Patient has previous malignancies other than breast cancer except:
• adequately treated in situ carcinoma of cervix;
• localized basal or squamous cell carcinoma of skin; or
• any previous malignancy treated with curative intent with recurrence risk of less than 30%.
• Patient is unable to understand informed consent or is unlikely to be compliant with protocol.

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (4)

Lombardi Cancer Institute, Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Siteman Cancer Center, Washington University

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Marcom PK, Isaacs C, Harris L, Wong ZW, Kommarreddy A, Novielli N, Mann G, Tao Y, Ellis MJ. The combination of letrozole and trastuzumab as first or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers. Breast Cancer Res Treat. 2007 Mar;102(1):43-9. doi: 10.1007/s10549-006-9307-8. Epub 2006 Aug 8.

  PMID: 16897431 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Paul K Marcom, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Matthew J Ellis, MB, PhD

  Washington University School of Medicine

  STUDY DIRECTOR

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: August 24, 2005
• First Posted: August 25, 2005
• Study Start: January 1, 2000
• Primary Completion: January 1, 2005
• Study Completion: July 1, 2005
• Last Updated: September 16, 2014

Record last verified: 2012-10

Locations

US (4)