Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Therapeutic Estradiol and Exemestane in Treating Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT01385280
First received: June 22, 2011
Last updated: April 11, 2014
Last verified: April 2014

June 22, 2011
April 11, 2014
February 2011
October 2013   (final data collection date for primary outcome measure)
Any incidence of grade 4 toxicity [ Time Frame: By day 90 ] [ Designated as safety issue: Yes ]
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
Same as current
Complete list of historical versions of study NCT01385280 on ClinicalTrials.gov Archive Site
  • Change in serum M-30 with treatment [ Time Frame: At baseline and on days, 8, 30, 60, and 90 ] [ Designated as safety issue: No ]
  • Change in CTC number with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ] [ Designated as safety issue: No ]
  • Change in CTC M-30 with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ] [ Designated as safety issue: No ]
  • Change in CTC ER expression with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ] [ Designated as safety issue: No ]
  • Change in CTC IGF1R expression with treatment [ Time Frame: At baseline and on days 8, 90, and 180 ] [ Designated as safety issue: No ]
  • Median time from entry on study to progression of disease [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]
    In weeks
Same as current
Not Provided
Not Provided
 
Therapeutic Estradiol and Exemestane in Treating Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer
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

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

OBJECTIVES:

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.

Interventional
Not Provided
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Estrogen Receptor-positive Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Biological: therapeutic estradiol
    Given orally (PO)
    Other Names:
    • Aquadiol
    • Dimenformon
    • Diogyn
    • Diogynets
    • ESDL
  • Drug: exemestane
    Given PO
    Other Names:
    • Aromasin
    • FCE-24304
    • PNU 155971
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: enzyme-linked immunosorbent assay
    Correlative studies
    Other Name: ELISA
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.
Interventions:
  • Biological: therapeutic estradiol
  • Drug: exemestane
  • Other: laboratory biomarker analysis
  • Other: enzyme-linked immunosorbent assay
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
Not Provided
October 2013   (final data collection date for primary outcome measure)

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 ineligible
  • 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 years
  • Known untreated brain or CNS metastases due to the risk of bleeding on aspirin during estradiol
  • 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
Female
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01385280
10-0906-04, NCI-2010-02366
Yes
University of Arizona
University of Arizona
National Cancer Institute (NCI)
Principal Investigator: Robert Livingston University of Arizona
University of Arizona
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP