Pilot Clinical Trial of Short-Term Bisphosphonate Administration as Chemoprevention for Breast Cancer Via Engagement of γδ T Cells

University of Wisconsin, Madison1 site in 1 country6 target enrollmentAugust 5, 2016

ConditionsBreast Neoplasms

InterventionsAlendronate

DrugsAlendronate

Overview

Phase: Phase 1
Intervention: Alendronate
Conditions: Breast Neoplasms
Sponsor: University of Wisconsin, Madison
Enrollment: 6
Locations: 1
Primary Endpoint: Percentage change of γδ T cell in CNB
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this study is to mechanistically define the potential anticancer activities of the osteoporosis bisphosphonate (BP) drug alendronate, and extend the analysis to learn novel information about the impact of BP on gamma delta (γδ) T cells in breast tissues as well as epithelial breast cell differentiation of high-risk women. To this end, we have designed a BP "window trial" to examine the effect of 1 - 3 weeks administration of alendronate on women at high-risk for breast cancer, at the level of immunosurveillance and mammary epithelial cell differentiation.

Registry

clinicaltrials.gov

Start Date

August 5, 2016

End Date

December 12, 2018

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

University of Wisconsin, Madison

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients referred for risk reduction mastectomy (eg. BRCA or other high-risk gene mutations, strong family history of breast cancer, prior or current LCIS, ADH, ALH and DCIS undergoing bilateral mastectomy or prophylactic contralateral mastectomy), oe patients at high-risk for breast cancer (eg. BRCA or other high-risk gene mutations, strong family history of breast cancer, prior or current LCIS, ADH, ALH and DCIS) who are not planning for immediate risk reduction mastectomy and are undergoing routine follow-up.
•Patients who are premenopausal defined as an individual with at least six menstrual cycles in the past year, women with hysterectomy with intact functioning ovaries who are not having menstrual cycles need to be 45 years of age and under.
•Patients must be 18 years of age or older
•The effects of Alendronate on the developing fetus are unknown. For this reason, sexually active heterosexual women must agree to use an effective form of birth control for the duration of study participation. Women who are NOT having 1) a hysterectomy, 2) fallopian tubes removed and/or 3) ovaries removed at the time of their breast surgery will also be required to use an effective form of birth control for 56 days following the last dose of study medication. In addition to, premenopausal women who are undergoing routine follow up and are not having surgery will be required to use an effective form of birth control for 56 days following the last dose of study medication. One of the following methods of birth control must be used by sexually active women of childbearing potential:
•Oral contraceptive pill in continuous use for \>90 days prior to study entry
•Vaginal ring in continuous use for \>90 days prior to study entry
•Skin patch in continuous use for \>90 days prior to study entry
•Injection in continuous use prior to study entry
•Diaphragm, cervical cap, or cervical shield with spermicide
•Contraceptive sponge

Exclusion Criteria

•Patients with a previous diagnosis of invasive breast cancer
•Patients who are post-menopausal (defined as 12 consecutive months without a menstrual period).
•Patients with an implant in the sampled breast
•Pregnant or lactating women are excluded from this study. Breastfeeding must be discontinued for the duration of study participation and for 8 weeks after the last dose of the study agent
•Patients for whom English is not their native language
•Patients with current or previous bisphosphonate therapy
•Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of alendronate and other bisphosphonates.
•Patients with esophageal dysmotility
•Patients unable to sit up or stay up for 30 minutes after taking oral dose
•Patients who have taken non-steroidal anti-inflammatory drugs (NSAIDs) in the past two weeks

Arms & Interventions

Alendronate

Subjects will take the study drug alendronate, a nitrogenous bisphosponate, for approximately one to three weeks before their breast surgery.

Intervention: Alendronate

Outcomes

Primary Outcomes

Percentage change of γδ T cell in CNB

Time Frame: 1-3 weeks

γδ T cell infiltration and activation as defined by the presence and increase in percentage of γδ T cells in the CNB sample following study agent (alendronate) administration. The effect of alendronate will be assessed using a one-tailed one-sample paired t-test or Wilcoxon signed rank test at a significance level of 0.10.

Secondary Outcomes

Percentage change of mammary luminal cells in the CNB samples after alendronate administration(1-3 weeks)
Percentage change of mammary epithelial basal cells in the CNB samples after alendronate administration(1-3 weeks)