Drug Withdrawal in Women With Progressive Breast Cancer While on Aromatase Inhibitor Therapy

Breast Cancer Clinical Trial

Official title:

A Phase II Clinical Trial of Drug Withdrawal in Women With Progressive Breast Cancer While on Aromatase Inhibitor Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00916162
• Other study ID #: 06-091
• Status: Completed
• Phase: N/A
• First received: June 5, 2009
• Last updated: May 7, 2013
• Start date: August 2006
• Est. completion date: January 2010

Study information

• Verified date: May 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this research study is to study the effects of stopping aromatase inhibitory (AI) therapy on breast cancer progression. Aromatase inhibitors are a class of drugs used to treat breast cancer in postmenopausal women. They work by decreasing the level of estrogen, which is believed to stimulate the growth of tumor tissue. Breast cancer that progresses despite therapy with an AI is thought to have been resistant to AI therapy. There is scientific evidence to suggest that resistant breast cancer cells learn to grow at the very low levels of estrogen present on AI therapy and that increasing estrogen levels even slightly by stopping AI therapy with inhibit the breast cancer cells. An improvement or stabilization of breast cancer has been observed after stopping therapy with tamoxifen, a different anti-estrogen therapy, and has been reported in the literature after stopping AI therapy. This research study will be the first study to formally test the rate of disease improvement (response) or stabilization after stopping AI therapy.

Description:

• Participants will have the following tests and procedures done at 8 weeks, 16 weeks, and 24 weeks after stopping AI therapy: Physical examination; blood tests; tumor assessment by physical exam (if possible); chest x-ray or CT scan of chest; CT scans of abdomen and pelvis; and bone scan.

• After week 24, these procedures will be repeated every 12 weeks while the participant is on the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with radiographically documented progressive or recurrent local-regional or metastatic disease. Disease must not be considered amenable to curative treatment

• Evidence of hormone sensitivity (ER +ve and/or PR +ve) of primary or secondary tumor tissue

• Measurable or nonmeasurable (but evaluable-defined as nontarget lesions) disease according to modified RECIST. Patients with bone disease are eligible. These patients will be evaluable only for the presence of stable or progressive disease and not a PR or CR. Patients wih bone-only metastatic disease will be considered to have stable disease if there is no evidence of new lesions and no clear progression of existing lesions

• Postmenopausal, defined as fulfilling any of the following criteria: If > 50 year, no menses within past 12 months, OR if < 50 years, no menses within past 12 months AND FSH within post menopausal range OR bilateral oophorectomy

• Current AI monotherapy at the time of documented disease progression

• AI therapy must be discontinued at time of study entry or no longer than two weeks prior to study entry

• Subjects receiving AI therapy for metastatic disease at the time of progression, must have had a prior radiographic documented response to AI therapy or have been on therapy for at least 6 months

• Subjects receiving AI as adjuvant therapy at the time of recurrence, must have been treated with AI therapy for at least 12 months

• Prior antiestrogen therapies including tamoxifen, steroidal AIs, nonsteroidal AIs, or faslodex in either the adjuvant or metastatic settings are allowed provided the patient is currently on AI monotherapy (or within two weeks of discontinuation) and has demonstrated a response or stable disease on the current AI

• Female

• Greater than 35 years of age

• ECOG performance status of 0, 1, or 2

Exclusion Criteria:

• Premenopausal

• Presence of life threatening metastatic disease, defined as extensive hepatic involvement, any part or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread. Subjects with discrete pulmonary parenchymal metastases will not be excluded, as long as their respiratory function is not compromised as a result of pulmonary metastatic disease

• Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician

• Prior or planned radiation therapy to single site of evaluable disease in the event that the site is the only site of evaluable disease

• AST or ALT greater than 5 times the upper limit of normal in teh presence of documented liver metastases

• Any severe concomitant condition believed to render subject undesirable for participation

• Systemic anticancer therapy including trastuzumab, chemotherapy, or other biologic agents after discontinuation of AI therapy

• Hormone replacement therapy including topical or vaginal estrogen therapy within 3 months prior to discontinuation of AI therapy

• Chronic bisphosphonates for hypercalcemia or for prevention of bone metastases; bisphosphonate therapy at the time of enrollment for documented bone metastases must be continued

• Previous or current systemic malignancy within the past five years except for contralateral breast carcinoma, in situ carcinoma of the cervix treated by cone biopsy, or adequately treated basal or squamous cell carcinoma of the skin. Solid tumors treated greater than 5 years ago and presumed cured are eligible

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Substance Withdrawal Syndrome

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the clinical benefit rate (CBR) after withdrawal of AI therapy in women with progressive or recurrent breast cancer while on AI therapy.		4 years	No
Secondary	To estimate time-to-progression (TTP) after withdrawal of AI therapy in women with progressive or recurrent breast cancer while on AI therapy.		4 years	No
Secondary	To estimate the objective response rate (CR or PR) in patients who have measurable disease as defined by RECIST at baseline.		4 years	No