Clinical Trial: Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment (ALTERNATE) in Postmenopausal Women: A Phase III Study

Brief Summary: 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.

Detailed Summary:

This clinical trial was designed to examine the pathologic outcomes of patients whose neoadjuvant treatment course is determined using an early marker of endocrine resistance (namely, Ki67 after 4 or 12 weeks of neoadjuvant therapy) as well as assessing clinical outcome of patients whose disease burden after completing neoadjuvant endocrine therapy is classified as Modified PEPI 0.

The primary and secondary objectives for the study are described below.

Primary Objectives:

  1. To determine whether fulvestrant administered for 24 weeks as neoadjuvant endocrine treatment decreases the proportion of endocrine resistant tumors* relative to patients treated with anastrozole.
  2. To determine whether fulvestrant in combination with anastrozole, administered for 24 weeks as neoadjuvant endocrine treatment, decreases the proportion of endocrine resistant tumors* relative to patients treated with anastrozole.
  3. To assess whether the 5 year RFS rate among women with a modified preoperative endocrine prognostic index (PEPI) score of 0 following 24 weeks of neoadjuvant anastrozole treatment is at least 95%.
  4. To assess whether the 5 year RFS rate among women with a modified PEPI score of 0 following 24 weeks of neoadjuvant fulvestrant, or fulvestrant in combination with anastrozole, is at least 95%. Note that this objective will only be tested if the selected fulvestrant arm was shown to be superior to anastrozole in objective 1 or 2.

Endocrine resistant tumor is defined by any one of the following criteria*:

  • Ki67> 10% after
    Sponsor: Alliance for Clinical Trials in Oncology

    Current Primary Outcome:

    • Rate of endocrine resistant disease-(First Phase) [ Time Frame: Up to 24 weeks ]
    • Pathologic complete response rate-(pCR rate) [ Time Frame: Up to 24 weeks ]
    • Recurrence-free survival (RFS)-(Second Phase) [ Time Frame: Up to 5 years ]


    Original Primary Outcome:

    • Rate of endocrine resistant disease - (Neo-adjuvant Phase) [ Time Frame: 7 years from study opening ]
    • Recurrence-free survival (RFS) - (Post surgery Phase) [ Time Frame: 8.5 to 11 years from study opening ]


    Current Secondary Outcome:

    Original Secondary Outcome: Pathologic complete response rate - (pCR rate) [ Time Frame: 7 years from study opening ]

    Information By: Alliance for Clinical Trials in Oncology

    Dates:
    Date Received: September 25, 2013
    Date Started: December 2013
    Date Completion:
    Last Updated: May 17, 2017
    Last Verified: May 2017