Alliance A011106

ALTernate approaches for clinical stage II or III Estrogen Receptor positive breast cancer NeoAdjuvant TrEatment (ALTERNATE) in postmenopausal women: A Phase III Study

The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer and stop it from growing. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body.

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:

•  Female ≥ 18 years of age
•  ECOG performance status 0-2
•  Postmenopausal, verified by:
• Post bilateral surgical oophorectomy, or
• No spontaneous menses > 1 year or
• No menses for < 1 year with FSH and estradiol levels in postmenopausal range, according to institutional standards
• Pathologic confirmation of invasive breast cancer diagnosed by core needle biopsy
• The extent of disease is a solitary lesion where the lesion is:
•  palpable
•  its size can be measured bidimensional by tape, ruler or caliper technique, and
•  its largest tumor diameter is at least 2.0 cm (that is considered measurable by the WHO criteria)

Treatment:

If you are randomized to treatment Group II (fulvestrant): You will receive two injections of fulvestrant into the muscle of your buttocks (one injection in each buttock) on Days 1 and 15 of the first treatment cycle, and then on Day 1 of every 4-week cycle after that, for a total 22 - 24 weeks (6 cycles).

If you are randomized to treatment Group III (anastrozole + fulvestrant): You will take 1 anastrozole tablet once each day for 22 - 24 weeks (6 cycles). The last tablet will be taken the day before your surgery. Take the anastrozole by mouth, with a large glass of water (8 ounces) with or without food. You will also receive two injections of fulvestrant into the muscle of your buttocks (one injection into each buttock) on Days 1 and 15 of the first treatment cycle, and on Day 1 of every 4-week cycle after that, for a total 22-24 weeks (6 cycles). If you miss a dose of anastrozole, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and take your regularly scheduled dose. Do not take two doses in the same day.