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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

Phase 2
18 Years
Not Enrolling

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Trial Information

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

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

Inclusion Criteria:

1. All subjects must be female

2. Postmenopausal status, defined as any one of the following criteria:

1. documented history of bilateral oophorectomy;

2. age 60 years or more;

3. ages 45 to 59 and satisfying one or more of the following criteria:

- amenorrhea for at least 12 months and intact uterus;

- amenorrhea for less than 12 months and a follicle stimulating hormone (FSH)
concentration within premenopausal range including:

- patients who have had a hysterectomy;

- patients who have received hormone replacement.

3. Patients must have histologically confirmed invasive breast cancer with a primary
tumor of 3 cm or more in greatest dimension as measured by clinical examination.

4. Estrogen receptor and/or progesterone receptor positive disease

5. Patients must not have received any prior treatment for current or newly diagnosed
breast cancer.

6. Patients must have not received previous treatment with any of the study medications
or similar drugs.

7. No use of selective estrogen receptor modulators (SERM) such as raloxifene or similar
agents in the past 2 years.

8. World Health Organization (WHO) performance status of 0, 1, or 2

9. Adequate organ function defined as follows:

1. adequate renal function, defined by a serum creatinine within 3 times the upper
limits of normal;

2. adequate liver function, defined by total bilirubin, AST, ALT, and alkaline
phosphatase within 3 times the upper limits of normal;

3. adequate bone marrow function, defined as a white blood cell (WBC) > 3.0 ml,
platelet (PLT) > 75,000/ul, hemoglobin (Hb) > 9 gm/l

10. Willing to undergo breast core biopsies as required by the study protocol

11. Ability to understand and sign a written informed consent for participation in the

12. Life expectancy of at least 1 year.

Exclusion Criteria:

1. Known severe hypersensitivity to Iressa or any of the excipients of this product

2. Premenopausal status

3. Patients with synchronous bilateral breast cancer

4. Patients with diffuse tumors that cannot be clearly measurable, such as inflammatory
breast cancer

5. Other coexisting malignancies with the exception of basal cell carcinoma or cervical
cancer in situ

6. Patients with brain metastasis

7. WHO performance status of 3 or 4

8. As judged by the investigator, uncontrolled intercurrent illness including, but not
limited to: ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, significant cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

9. Evidence of any other significant clinical disorder or laboratory finding that makes
it undesirable for the subject to participate in the clinical trial.

10. Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St. John's

11. Concurrent treatment with estrogens or progestins. Patients must stop these drugs at
least two weeks prior to study entry.

12. Treatment with a non-approved or investigational drug within 30 days before Day 1 of
study treatment

13. Platelet count less than 75,000

14. In the opinion of the investigator, bleeding diathesis or anticoagulation therapy
that would preclude intramuscular injections.

15. History of hypersensitivity to castor oil

16. Any evidence of clinically active interstitial lung disease (patients with chronic
stable radiographic changes who are asymptomatic need not be excluded).

17. Patients with recurrent breast cancer. Patients with contralateral second primary
breast cancers are eligible.

Type of Study:


Study Design:

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

Outcome Measure:

Primary study objective - To determine the clinical response rate of primary breast cancer to the combination of Arimidex, Faslodex, and Iressa

Outcome Time Frame:

until disdase progression

Safety Issue:


Principal Investigator

Mothaffar Rimawi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor Breast Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2003

Completion Date:

September 2006

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms



Baylor Breast Center Houston, Texas  77030