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Pilot Study Estradiol Followed by Exemestane Hormone Receptor + Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT01385280
Recruitment Status : Completed
First Posted : June 30, 2011
Results First Posted : October 17, 2018
Last Update Posted : October 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona

Tracking Information
First Submitted Date  ICMJE June 22, 2011
First Posted Date  ICMJE June 30, 2011
Results First Submitted Date  ICMJE July 2, 2018
Results First Posted Date  ICMJE October 17, 2018
Last Update Posted Date October 17, 2018
Study Start Date  ICMJE February 2011
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
Number of Participants With Grade 4 Toxicity [ Time Frame: By day 90 ]
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
Original Primary Outcome Measures  ICMJE
 (submitted: June 29, 2011)
Any incidence of grade 4 toxicity [ Time Frame: By day 90 ]
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
Change History Complete list of historical versions of study NCT01385280 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
  • Patients With Change in Serum M-30 (a Marker of Mitochondrial Apoptosis) With Treatment [ Time Frame: At baseline and on days, 8, 30, 60, and 90 ]
  • Patients With Change in Number of Circulating Tumor Cells (CTC) With Treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
  • Patients With Change in Circulating Tumor Cells (CTC) Expression of M-30 With Treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
  • Change in Circulating Tumor Cells (CTC) ER Expression With Treatment [ Time Frame: At baseline and on days 8, 90, and 180 ]
  • Change in Circulating Tumor Cells (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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2011)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study Estradiol Followed by Exemestane Hormone Receptor + Metastatic Breast Cancer
Official Title  ICMJE 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
Brief Summary

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

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Estrogen Receptor-positive Breast Cancer
  • Progesterone Receptor Positive Tumor
  • Recurrent Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Biological: therapeutic estradiol
  • Drug: exemestane
  • Other: laboratory biomarker analysis
  • Other: enzyme-linked immunosorbent assay
Publications * Chalasani P, Stopeck A, Clarke K, Livingston R. A pilot study of estradiol followed by exemestane for reversing endocrine resistance in postmenopausal women with hormone receptor-positive metastatic breast cancer. Oncologist. 2014 Nov;19(11):1127-8. doi: 10.1634/theoncologist.2014-0306. Epub 2014 Sep 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2015)
13
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2011)
15
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Follicle-stimulating hormone (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 (any 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01385280
Other Study ID Numbers  ICMJE 10-0906-04
NCI-2010-02366 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
3P30CA023074 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Arizona
Study Sponsor  ICMJE University of Arizona
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Robert Livingston University of Arizona
PRS Account University of Arizona
Verification Date September 2018

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