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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

Open (Enrolling)
Estrogen Receptor-positive Breast Cancer, Progesterone Receptor-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

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Trial Information

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


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.

Inclusion Criteria:

- Post-menopausal women with metastatic carcinoma of the breast; post-menopausal, as
defined by at least one of the following: at least 12 months without spontaneous
menstrual bleeding, history of bilateral salpingo-oophorectomy with or without
hysterectomy, age > 55 with hysterectomy with or without oophorectomy, serum FSH in
post-menopausal range within 4 weeks of registration

- Positive for estrogen receptor (ER) or progesterone receptor (PgR) with positivity
defined as immunohistochemical staining in >= 10% of cells

- Either measurable disease by RECIST or non-measurable evaluable disease; tests to
evaluate disease (measurable and non-measurable) must be completed within 28 days
prior to registration; these will include a CT scan of the chest/abdomen/pelvis and a
bone scan; patients with effusions or ascites as the only sites of disease are

- Performance status of 0-2 by Zubrod criteria

- Patients must have a baseline CA15-3 or CA 27.29 measurement for future comparison,
but any baseline value is acceptable

- Patients must have had prior aromatase inhibitor (AI) therapy in the metastatic
setting (oneany number of prior AI is allowed, this may have been any of the AI's),
or have developed metastatic disease on adjuvant AI therapy; prior treatment with
tamoxifen and/or fulvestrant is also allowed; patients must not have been previously
treated with estradiol for metastatic breast cancer

- Patients must be able to take oral medications

- Patients must be informed of the investigational nature of this study and give
written informed consent in accordance with institutional and federal guidelines

- Patients must consent to the serum and CTC blood specimen submissions

Exclusion Criteria:

- Planning to receive concomitant chemotherapy, hormone therapy (including hormone
replacement therapy), radiation therapy, or antibody therapy for malignancy while
receiving protocol treatment, with the single exception of trastuzumab; concomitant
trastuzumab will be allowed for Her-2 positive patients who were previously on
trastuzumab; patients who have had previous radiotherapy must complete treatment
within 4 weeks of registration, and have recovered from acute toxicity from
radiation; patients with prior cytotoxic chemotherapy for metastatic disease will not
be eligible

- Known hypersensitivity or intolerance to estradiol, aromatase inhibitors, or aspirin;
patients must not have a history of aspirin-induced GI bleeding within the past 3

- Known untreated brain or CNS metastases due to the risk of bleeding on aspirin during

- History of deep vein thrombosis, pulmonary embolism, or other clot requiring
anticoagulation; patients must not have a known inherited hypercoagulable disorder

- History of decompensated congestive heart failure, unstable angina, or uncontrolled
psychiatric illness which would limit compliance with the protocol treatment

- Prior malignancy except for the following: adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer
from which the patient is currently in complete remission, or any other cancer from
which the patient has been disease-free for 5 years

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Any incidence of grade 4 toxicity

Outcome Description:

Such as deep vein thrombosis requiring hospitalization or pulmonary embolism

Outcome Time Frame:

By day 90

Safety Issue:


Principal Investigator

Robert Livingston

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Arizona


United States: Food and Drug Administration

Study ID:




Start Date:

February 2011

Completion Date:

Related Keywords:

  • Estrogen Receptor-positive Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



University of Arizona Cancer Center Tucson, Arizona  85724