Arimidex/Faslodex/Iressa Study: A Trial Using Arimidex, Faslodex and Iressa in Women With Breast Cancer

BREAST CANCER Clinical Trial

Official title: Arimidex/Faslodex/Iressa Study: A Phase II Trial of Primary Systemic Therapy Using a Combination of Arimidex, Faslodex and Iressa (Gefitinib) in Postmenopausal Women With Hormone Receptor Positive Breast Cancer

Status Terminated

Clinical Trial Summary

The investigators want to know if combining Arimidex and Faslodex with Iressa will be an effective treatment for breast cancer. They also want to know, using special tests on the tumor, the changes that occur with the treatment so they can try to improve their treatment for breast cancer in the future.

Clinical Trial Description

Over the last three decades, a steady shift has occurred in the management of breast cancer. Because it was traditionally viewed as a local disease, many advocated the use of radical surgery to achieve maximum survival benefit. This view has been slowly replaced by a broader biologic view that recognizes the often systemic nature of breast cancer, even when it appears to be localized to the breast. Results from randomized clinical trials have demonstrated that less extensive surgery or lumpectomy plus radiation therapy are optimal for local management of early breast cancer. In addition to the less radical approach to surgical treatment of breast cancer, other randomized clinical trials established the value of postoperative (adjuvant) systemic therapy in improving overall survival by eradicating micrometastatic disease, the major cause of mortality from breast cancer. An improved survival has been shown from using chemotherapy as well as the antiestrogen tamoxifen in the adjuvant setting and has been confirmed through the overview analyses from the Early Breast Cancer Trialist Collaborative Group. Despite the well-documented benefits of adjuvant systemic therapy, it is not effective in preventing death from breast cancer in all patients who are candidates for such treatment. The worth of such therapy can only be judged in retrospect upon disease relapse, a time when breast cancer is nearly always incurable. Currently, there are few reliable methods to predict the success or failure of a particular postoperative treatment modality and better ways to predict and optimize outcome are needed. Preoperative (primary, neoadjuvant) systemic therapy is an alternative approach that is based on a strong rationale. With the tumor still in place and directly accessible, this form of therapy allows direct observation of response to treatment which may predict the likelihood of controlling distant micrometastatic disease and also enables the sampling of tissue to explore molecular correlates of response and also the mechanisms of action of therapeutic agents. Furthermore, it allows early identification of patients with refractory disease who might benefit from alternative treatments before they develop macrometastatic disease and miss the opportunity for a cure. Primary systemic therapy can also help facilitate surgery and debulking of disease in those patients with initially inoperable tumors, as well as improve the odds of breast conservation.

A pivotal trial that established the role of preoperative systemic therapy was the NSABP trial B-187. In this trial, women with localized breast cancer were randomized to receive Adriamycin, Cytoxan (AC) either preoperatively or postoperatively. There was no difference between the two groups in disease-free and overall survival. Furthermore, quantifying tumor response preoperatively allowed prediction of patient outcome in terms of disease-free and overall survival. Specifically, patients achieving a pathologic complete response, i.e., complete disappearance of invasive cancer on pathologic examination, had the best outcome, establishing the role of response as a valid surrogate predictor of the sensitivity of distant micrometastatic disease to chemotherapy and subsequent clinical outcome. In addition, breast-conserving surgery was more frequently performed in the preoperative treatment group, an advantage over the postoperative treatment approach. Most importantly, however, NSABP trial B-18 showed conclusively that primary systemic therapy is safe and does not place patients at a disadvantage by delaying primary surgical treatment. Another large, multicenter prospective trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) confirmed the findings of NSABP trial B-18.

Primary study objective:

• To determine the clinical response rate of primary breast cancer to the combination of Arimidex, Faslodex, and Iressa

Secondary study objectives:

• To study molecular changes in response to treatment

• To determine the pathologic response rate

• To assess the tolerability and safety of the combination regimen ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• BREAST CANCER
• Breast Neoplasms

• NCT number: NCT00206414
• Study type: Interventional
• Source: Baylor Breast Care Center
• Status: Terminated
• Phase: Phase 2
• Start date: January 2003
• Completion date: September 2006