Pilot Study Estradiol Followed by Exemestane Hormone Receptor + Metastatic Breast Cancer
|ClinicalTrials.gov Identifier: NCT01385280|
Recruitment Status : Completed
First Posted : June 30, 2011
Last Update Posted : December 3, 2015
RATIONALE: Estrogen can cause the growth of tumor cells. Hormone therapy using therapeutic estradiol may fight breast cancer by lowering the amount of estrogen the body makes. Though estradiol initially produces stimulation of ER+ cancer cells, both laboratory and some clinical experience indicate that it may have the opposite effect on such cells, once they have become resistant to estrogen deprivation. In laboratory models, there is death of the "resistant" population after estradiol treatment, followed by restoration of sensitivity of the remaining cells to estrogen deprivation, as with an aromatase inhibitor. Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving therapeutic estradiol together with exemestane may kill more tumor cells.
PURPOSE: This clinical trial studies therapeutic estradiol and exemestane in treating post-menopausal patients with hormone receptor-positive metastatic breast cancer
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor-positive Breast Cancer Progesterone Receptor Positive Tumor Recurrent Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer||Biological: therapeutic estradiol Drug: exemestane Other: laboratory biomarker analysis Other: enzyme-linked immunosorbent assay||Not Applicable|
I. To assess feasibility and toxicity associated with estradiol followed by exemestane in the treatment of estrogen receptor positive metastatic breast cancer patients failing prior aromatase inhibitor therapy.
II. Exploratory analysis of bio-correlates which will evaluate the mechanism of action of this treatment combination: changes in serum M-30, a marker of mitochondrial apoptosis; changes in number of circulating tumor cells (CTC); changes in CTC expression of ER, IGF1-R, and M-30.
III. Exploratory analysis of Progression Free Survival (PFS).
OUTLINE: Patients receive oral therapeutic estradiol once daily on days 1-3, twice daily on days 4-7, and thrice daily on days 8-90. Beginning on day 98, patients receive oral exemestane once daily in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study Of Estradiol Followed By Exemestane For Post-Menopausal Hormone Receptor Positive Metastatic Breast Cancer After Prior Failed Endocrine Therapy: Reversing Endocrine Resistance|
|Study Start Date :||February 2011|
|Actual Primary Completion Date :||January 2013|
|Actual Study Completion Date :||October 2013|
Experimental: Arm I
Patients receive oral therapeutic estradiol once daily on days 1-3, twice daily on days 4-7, and thrice daily on days 8-90. Beginning on day 98, patients receive oral exemestane once daily in the absence of disease progression or unacceptable toxicity. Also laboratory biomarker analysis and enzyme-linked immunosorbent assay will be taken for correlative studies.
Biological: therapeutic estradiol
Given orally (PO)
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other Name: ELISA
- Any incidence of grade 4 toxicity [ Time Frame: By day 90 ]Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
- Change in serum M-30 with treatment [ Time Frame: At baseline and on days, 8, 30, 60, and 90 ]
- Change in CTC number with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
- Change in CTC M-30 with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
- Change in CTC ER expression with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
- Change in CTC IGF1R expression with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
- Median time from entry on study to progression of disease [ Time Frame: Up to 1.5 years ]In weeks
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01385280
|United States, Arizona|
|University of Arizona Cancer Center|
|Tucson, Arizona, United States, 85724-5024|
|Principal Investigator:||Robert Livingston||University of Arizona|