Anti-Hormone Therapy (With Anastrazole and Fulvestrant) Before Surgery to Treat Postmenopausal Women With Breast Cancer.

• ClinicalTrials.gov Identifier: NCT00921115
• Recruitment Status: Active, not recruiting
• First Posted: June 16, 2009
• Results First Posted: May 18, 2017
• Last Update Posted: June 13, 2022
• Sponsor: University of Kansas Medical Center
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): University of Kansas Medical Center

Study Description

Brief Summary:

This study is being done to test the safety and effectiveness of two drugs, Anastrozole and Fulvestrant, used as combined therapy in the neo-adjuvant setting for hormone receptor positive invasive breast cancer.

Condition or disease	Intervention/treatment	Phase
Invasive Breast Cancer	Drug: Fulvestrant; Drug: Anastrazole	Phase 2

Detailed Description:

Hormonal therapies are generally preferred treatments of breast cancer because they have minimal side effects. Hormone receptor positive breast cancer generally does not respond very well to chemotherapy, which has many side effects. Hormonal therapy with a single drug such as Anastrozole is the main type of treatment used to reduce the risk of cancer recurrence. Whether a combination of Anastrazole nad Fulvestrant is effective and feasible is not known. This study is being done to answer this question.

This is a phase II single arm study. Patients will have an Oncotype Dx performed and only if the recurrence score is low or intermediate, they would be eligible. Eligible patients will receive Anastrazole and Fulvestrant for 16 week.

Subjects will receive Anastrazole 1 mg po q day and Fulvestrant 500 mg IM, day 1, day 14, day 28 and thereafter once every 28 days on outpatient basis. On day 28, subjects will be evaluated for side effects and clinically and a needle core biopsy (optional) will be obtained. If there is increase in Ki 67 by 50%, subjects will be taken off the study. Response evaluation will occur every 28 days during outpatient clinic visits. All treatment will continue until 4 months when patients will undergo surgical intervention. After surgery, patients will be off study and will receive additional breast cancer therapy at the discretion of their treating physician. Patients who develop progressive disease on protocol will be removed from the study and will then be treated at the discretion of the treating physician. The protocol will be closed after the last accrued patient has had surgery.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combined Fulvestrant and Anastrozole as Neo-adjuvant Endocrine Therapy in Postmenopausal Women With Hormone Receptor Positive Invasive Breast Cancer
• Actual Study Start Date: May 2009
• Actual Primary Completion Date: April 2015
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Arimidex + Faslodex; Patients will have an Oncotype Dx performed and if the RS is <25, they will receive Anastrazole and Fulvestrant for 16 weeks. On day 28, subjects will be evaluated for side effects and a needle core biopsy (optional) will be obtained. Response evaluation will occur every 28 days. All treatment will continue for 4 months followed by breast surgery. After surgery, patients will be off study and will receive additional breast cancer therapy per their treating physician. Patients who develop progressive disease on protocol will be removed from the study and treated by their treating physician. The protocol will be closed after the last accrued patient has had surgery.

Drug: Fulvestrant; Fulvestrant IM on day 14 and on day 28 followed by day 28 of all subsequent cycles thereafter. Treatment will be continued for a total of 4 cycles.; Other Name: Faslodex; Drug: Anastrazole; Anastrazole, 1mg by mouth every day of all 28 day cycles and continued for a total of 4 cycles; Other Name: Arimidex

Outcome Measures

Primary Outcome Measures :

1. Pathologic Complete Response (PCR) Rate [ Time Frame: 4 months ]
   Pathologic complete response (PCR) rate with 4 months of neo-adjuvant combination endocrine therapy (Anastrazole and Fulvestrant).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria

• Female patient > 18 years of age.
• Histologically proven invasive adenocarcinoma of the breast.
• Patients must be candidates for neoadjuvant treatment (Tumor size > 2cm and/or clinical N1 or N2).
• ER positive (> 10% of cells) and/or PgR positive (> 10% of the cells) and HER-2 negative disease (IHC 0 or 1+ and/or FISH negative, IHC 2+ and FISH negative)

• Menopausal status

  • Patients must be post-menopausal as defined by one of the following criteria:

    • Prior bilateral oophorectomy
    • 12 months since LMP with no prior hysterectomy
    • Patients > 55 years with prior hysterectomy
    • Patients < 55 years of age and with a prior hysterectomy without oophorectomy, estradiol and FSH levels must be consistent with the patient being postmenopausal.
  • Premenopausal or perimenopausal women who do not meet the postmenopausal criteria above are also eligible, but are required to undergo ovarian suppression with an LHRH agonist. Ovarian suppression can be initiated any time prior to or on day 1 of protocol therapy and must continue throughout protocol therapy.
• Performance status of 2 or better per SWOG criteria
• No prior chemotherapy or endocrine therapy for the current cancer diagnosis.
• If female of childbearing potential, pregnancy test is negative prior to initiation of ovarian suppression.
• Patients must be informed of the investigational nature of the study, and must sign an informed consent in accordance with the institutional rules.
• Oncotype Dx Recurrence Score </= 25.

Exclusion criteria

• Patients with metastatic disease.
• The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications.
• Premenopausal without ovarian suppression.
• Pregnancy or lactation.
• Patients with concomitant or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Patients with emotional limitations are excluded from study
• Platelets less than 100 x 109 /L
• Total bilirubin greater than 1.5 x ULRR
• ALT or AST greater than 2.5 x ULRR
• History of bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet therapy).
• History of hypersensitivity to active or inactive excipients of fulvestrant (i.e. castor oil or Mannitol).
• Oncotype Dx Recurrence Score of >25.

Contacts and Locations

Locations

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Sponsors and Collaborators

University of Kansas Medical Center

AstraZeneca

Investigators

• Principal Investigator: Qamar Khan, MD; University of Kansas Medical Center

More Information

• Responsible Party: University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT00921115
• Other Study ID Numbers: 11595; IRUSANAS0092 ( Other Identifier: Astra Zeneca )
• First Posted: June 16, 2009
• Results First Posted: May 18, 2017
• Last Update Posted: June 13, 2022
• Last Verified: May 2022

Keywords provided by University of Kansas Medical Center:

hormone receptor positive; invasive breast cancer; endocrine therapy; Anastrazole; Fulvestrant; breast tumors; postmenopausal

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Fulvestrant; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action