Estrogen Receptor-positive Breast CancerNCT01385280
Pilot Study Estradiol Followed by Exemestane Hormone Receptor + Metastatic Breast Cancer
A study testing therapeutic estradiol, exemestane and laboratory biomarker analysis in people with Estrogen Receptor-positive Breast Cancer and Progesterone Receptor Positive Tumor, run by University of Arizona at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer, Progesterone Receptor Positive Tumor, Recurrent Breast Cancer
- What is being tested?
- therapeutic estradiol, exemestane and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Oct 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arizona Cancer Center
Tucson, Arizona, 85724-5024
About this study
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
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
Read the detailed description
OBJECTIVES:
- 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.
- Conditions
- Estrogen Receptor-positive Breast Cancer, Progesterone Receptor Positive Tumor, Recurrent Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
- Being tested
- therapeutic estradiol, exemestane, laboratory biomarker analysis, enzyme-linked immunosorbent assay
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic estradiolBiological
Also called Aquadiol, Dimenformon, Diogyn, Diogynets
Given orally (PO)
exemestaneDrug
Also called Aromasin, FCE-24304, PNU 155971
Given PO
laboratory biomarker analysisOther
Correlative studies
enzyme-linked immunosorbent assayOther
Also called ELISA
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Biological: therapeutic estradiol; Drug: exemestane; Other: laboratory biomarker analysis; Other: enzyme-linked immunosorbent assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade 4 Toxicity
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
Measured: By day 90
Secondary outcomes (6)
Patients With Change in Serum M-30 (a Marker of Mitochondrial Apoptosis) With Treatment
Measured: At baseline and on days, 8, 30, 60, and 90
Patients With Change in Number of Circulating Tumor Cells (CTC) With Treatment
Measured: At baseline and on days 8, 90, and 180
Patients With Change in Circulating Tumor Cells (CTC) Expression of M-30 With Treatment
Measured: At baseline and on days 8, 90, and 180
Change in Circulating Tumor Cells (CTC) ER Expression With Treatment
Measured: At baseline and on days 8, 90, and 180
Change in Circulating Tumor Cells (CTC) IGF1R Expression With Treatment
Measured: At baseline and on days 8, 90, and 180
Median Time From Entry on Study to Progression of Disease
In weeks
Measured: Up to 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2011 (estimated)
- Study startFeb 2011
- Primary completionJan 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Robert Livingston, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385280
- Sponsor's protocol ID
- 10-0906-04
- Other IDs
- NCI-2010-02366, 3P30CA023074
- Status last verified
- Sep 2018
- First submitted
- 22 Jun 2011
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 25260365
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01385280
- Acronym / sponsor ID
- 10-0906-04
- Conditions
- Estrogen Receptor-positive Breast Cancer, Progesterone Receptor Positive Tumor, Recurrent Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 30 Jun 2011 (estimated)
- Results
- Posted 17 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: therapeutic estradiol, Drug: exemestane, Other: laboratory biomarker analysis, Other: enzyme-linked immunosorbent assayPatients 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. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| therapeutic estradiolAlso: Aquadiol, Dimenformon, Diogyn, DiogynetsGiven orally (PO) | Biological | Arm I |
| exemestaneAlso: Aromasin, FCE-24304, PNU 155971Given PO | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| enzyme-linked immunosorbent assayAlso: ELISACorrelative studies | Other | Arm I |
Primary outcome
Number of Participants With Grade 4 Toxicity
Time frame: By day 90
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
6 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25260365Chalasani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Livingston principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing therapeutic estradiol, exemestane and laboratory biomarker analysis in people with Estrogen Receptor-positive Breast Cancer and Progesterone Receptor Positive Tumor, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade 4 Toxicity (time frame: By day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01385280, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2018.