Breast CancerNCT00200174
Combined Estrogen Blockade of the Breast With Exemestane and Raloxifene in Postmenopausal Women With a History of Breast Cancer Who Have No Clinical Evidence of Disease
A study testing Raloxifene followed by combination therapy and Exemestane followed by combination therapy in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this research study is to learn about the effects of two drugs when they are given together. The names of the drugs are raloxifene and exemestane. Raloxifene is a drug that is related to estrogen. In the liver and bone, it acts like estrogen. In the breast and uterus it acts like an anti-estrogen. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Raloxifene followed by combination therapy and Exemestane followed by combination therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1999to Aug 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women with a history of AJCC Stage 0, I, II or III breast cancer, with no clinical evidence of disease, after completion of all planned adjuvant therapy. Patients must not have received anti-estrogen therapy as part of their adjuvant treatment. Patients with a history of invasive ER- and/or PR-positive breast cancer are eligible only if they have not received an anti-estrogen as part of adjuvant therapy, and they are at least 2 years from the time of their primary surgery.
- Patients must have completed all planned adjuvant therapy, including surgery, chemotherapy, and radiation therapy, at least 4 weeks prior to treatment. There is no limit as to the amount of time that may have passed since completion of adjuvant therapy and initiation of treatment.
- Patients must be postmenopausal, as defined by either:
- No spontaneous menses for at least 5 years; women who have had a hysterectomy in this group, but have intact ovaries must have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range
- Spontaneous menses within the past 5 years, but amenorrheic (e.g. spontaneous or secondary to chemotherapy, radiation therapy or hysterectomy) for at least 12 months, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range
- Bilateral oophorectomy
Show all 11Show fewer
- Patients must have a history of breast cancer confirmed by the Department of Pathology at Memorial Sloan-Kettering Cancer Center.
- Patients must be at least 18 years old, and must be able to give written informed consent.
- Karnofsky performance status > 80%.
- Laboratory parameters:
- WBC =>3.0 x 106 cells/ml serum bilirubin <= 1.5 mg/dl serum creatinine <= 1.5 mg/dl serum AST (SGOT) <= 2x upper institutional normal CEA and CA15-3 within institutional normal limits
Who cannot join
- Prior history of bilateral mastectomy.
- Prior history of ovarian or endometrial cancer.
- Prior or current history of osteoporosis, as defined by a lumbar-spine bone mineral density < 2.5 SD below the mean value for normal premenopausal women.
- Use of bisphosphonates or calcitonin within the past 3 months.
- Prior history of venous thrombosis or pulmonary embolism.
- Patients with unstable angina or New York Heart Association Class III or IV heart disease.
- Prior hormonal therapy within the past 3 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: Combined Estrogen Blockade of the Breast With Exemestane and Raloxifene in Postmenopausal Women With a History of Breast Cancer Who Have No Clinical Evidence of Disease: A Pilot Chemoprevention Trial
The purpose of this research study is to learn about the effects of two drugs when they are given together. The names of the drugs are raloxifene and exemestane.
Raloxifene is a drug that is related to estrogen. In the liver and bone, it acts like estrogen. In the breast and uterus it acts like an anti-estrogen. It has been used in postmenopausal women to prevent a disease called osteoporosis. This is a disease that decreases bone strength over many years and may finally lead to bone fractures. In a group of women who were taking the drug, it also seemed to decrease the chances of breast cancer and possibly endometrial cancer (cancer of the uterus). Therefore, we want to study it further to see if it prevents breast cancer. We also want to find out if it may be even better in preventing breast cancer if it is given with another drug.
The other drug in this trial is exemestane. Exemestane is a type of drug that works to decrease estrogen levels in postmenopausal women. This type of drug is used in women for the treatment of breast cancer. Before we can decide if the two drugs combined are better for preventing breast cancer, we must first test these drugs together to make sure that they are safe. This safety testing is the purpose of this trial.
Read the detailed description
The objectives of this project are to investigate the safety and toxicity of the combination of raloxifene, a selective estrogen receptor modulator (SERM), with exemestane, a new steroidal aromatase inhibitor, in postmenopausal women with a history of breast cancer who have no clinical evidence of disease. The study cohort will consist of postmenopausal women with a history of AJCC Stage 0, I, II, or III breast cancer after completion of all planned adjuvant therapy. The study cohort is limited to patients who have not already received anti-estrogen therapy as part of post-operative adjuvant treatment. Patients with a history of invasive ER- and/or PR-positive breast cancer are eligible only if they have not received an anti-estrogen as part of adjuvant therapy, and they are at least 2 years from the time of their primary surgery.
Tamoxifen has been shown to reduce the incidence of contralateral breast cancer regardless of the estrogen expression of the primary tumor and may therefore be offered as a chemopreventive agent to patients who have not received an anti-estrogen in the adjuvant setting. This population of patients is also a reasonable cohort in which to test other chemoprevention regimens. Our hypothesis is that the combination of raloxifene and exemestane may offer an alternative treatment for chemoprevention that may prove to be more effective than an anti-estrogen alone.
Endpoints of the study are to determine whether the combination of raloxifene and exemestane is safe and tolerable with respect to:
- markers of bone turnover and bone mineral density
- the serum lipoprotein profile
- quality of life (in particular, symptoms of estrogen deficiency)
- pharmacokinetics and pharmacodynamics of both drugs.
We will also determine the feasibility of using mammography and breast MRI imaging to assess the effects of the combination on radiographic breast density.
As part of a correlative laboratory study of breast biopsy material, women may undergo an optional biopsy of their unaffected breast. Breast biopsy material will be evaluated both pre- and 3 months post-treatment to determine whether the combination will have an impact on breast tissue aromatase activity and breast tissue estrogen levels, and potential surrogate endpoint biological markers.
- Conditions
- Breast Cancer
- Being tested
- Raloxifene followed by combination therapy, Exemestane followed by combination therapy
- Keywords
- Breast cancer, estrogen, postmenopausal
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raloxifene followed by combination therapyDrug
Patients will be randomized to either Raloxifene at 60mg P.O. (each day) for 2 weeks (time designated: week- 2) After two weeks of single agent therapy, patients will be started on combination therapy with oral raloxifene (60mg/day) and oral exemestane (25mg/day) (time designated week 0), and continued on both drugs for one year (month 12). Patients will be required to start supplemental calcium (900-1500 mg/day) plus vitamin D (400-600 units/day) P.O. each day during week 0.
Exemestane followed by combination therapyDrug
Patients will be randomized to Exemestane at 25mg P.O. for 2 weeks (time designated: week- 2) After two weeks of single agent therapy, patients will be started on combination therapy with oral raloxifene (60mg/day) and oral exemestane (25mg/day) (time designated week 0), and continued on both drugs for one year (month 12). Patients will be required to start supplemental calcium (900-1500 mg/day) plus vitamin D (400-600 units/day) P.O. each day during week 0.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Raloxifene followed by combination therapy Receives: Drug: Raloxifene followed by combination therapy |
| B | Active comparator | Exemestane followed by combination therapy Receives: Drug: Exemestane followed by combination therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a hx of AJCC Stage 0, I, II, or III breast cancer, who have no clinical evidence of disease, after completion of all planned adjuvant
Measured: 1 year
Secondary outcomes (1)
To determine the feasibility of using mammography and breast MRI imaging to assess the effects of raloxifene plus exemestane on radiographic breast density.
Measured: baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJul 1999
- Primary completionJul 2003
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacia
- Responsible party
- Sponsor
- Investigators
- Maura Dickler, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00200174
- Sponsor's protocol ID
- 99-017
- Status last verified
- Jul 2023
- First submitted
- 9 Sep 2005
- Last updated
- 5 Jul 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Estrogen Blockade of the Breast With Exemestane and Raloxifene in Postmenopausal Women With a History of Breast Cancer Who Have No Clinical Evidence of Disease: A Pilot Chemoprevention Trial
- ClinicalTrials.gov ID
- NCT00200174
- Acronym / sponsor ID
- 99-017
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, estrogen, postmenopausal
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Pharmacia
- Study start
- Jul 1999
- Primary completion
- Jul 2003 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to learn about the effects of two drugs when they are given together. The names of the drugs are raloxifene and exemestane.
Raloxifene is a drug that is related to estrogen. In the liver and bone, it acts like estrogen. In the breast and uterus it acts like an anti-estrogen. It has been used in postmenopausal women to prevent a disease called osteoporosis. This is a disease that decreases bone strength over many years and may finally lead to bone fractures. In a group of women who were taking the drug, it also seemed to decrease the chances of breast cancer and possibly endometrial cancer (cancer of the uterus). Therefore, we want to study it further to see if it prevents breast cancer. We also want to find out if it may be even better in preventing breast cancer if it is given with another drug.
The other drug in this trial is exemestane. Exemestane is a type of drug that works to decrease estrogen levels in postmenopausal women. This type of drug is used in women for the treatment of breast cancer. Before we can decide if the two drugs combined are better for preventing breast cancer, we must first test these drugs together to make sure that they are safe. This safety testing is the purpose of this trial.
Detailed description
The objectives of this project are to investigate the safety and toxicity of the combination of raloxifene, a selective estrogen receptor modulator (SERM), with exemestane, a new steroidal aromatase inhibitor, in postmenopausal women with a history of breast cancer who have no clinical evidence of disease. The study cohort will consist of postmenopausal women with a history of AJCC Stage 0, I, II, or III breast cancer after completion of all planned adjuvant therapy. The study cohort is limited to patients who have not already received anti-estrogen therapy as part of post-operative adjuvant treatment. Patients with a history of invasive ER- and/or PR-positive breast cancer are eligible only if they have not received an anti-estrogen as part of adjuvant therapy, and they are at least 2 years from the time of their primary surgery.
Tamoxifen has been shown to reduce the incidence of contralateral breast cancer regardless of the estrogen expression of the primary tumor and may therefore be offered as a chemopreventive agent to patients who have not received an anti-estrogen in the adjuvant setting. This population of patients is also a reasonable cohort in which to test other chemoprevention regimens. Our hypothesis is that the combination of raloxifene and exemestane may offer an alternative treatment for chemoprevention that may prove to be more effective than an anti-estrogen alone.
Endpoints of the study are to determine whether the combination of raloxifene and exemestane is safe and tolerable with respect to:
- markers of bone turnover and bone mineral density
- the serum lipoprotein profile
- quality of life (in particular, symptoms of estrogen deficiency)
- pharmacokinetics and pharmacodynamics of both drugs.
We will also determine the feasibility of using mammography and breast MRI imaging to assess the effects of the combination on radiographic breast density.
As part of a correlative laboratory study of breast biopsy material, women may undergo an optional biopsy of their unaffected breast. Breast biopsy material will be evaluated both pre- and 3 months post-treatment to determine whether the combination will have an impact on breast tissue aromatase activity and breast tissue estrogen levels, and potential surrogate endpoint biological markers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Raloxifene followed by combination therapyRaloxifene followed by combination therapy |
| B | Active comparator | Drug: Exemestane followed by combination therapyExemestane followed by combination therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Postmenopausal women with a history of AJCC Stage 0, I, II or III breast cancer, with no clinical evidence of disease, after completion of all planned adjuvant therapy. Patients must not have received anti-estrogen therapy as part of their adjuvant treatment. Patients with a history of invasive ER- and/or PR-positive breast cancer are eligible only if they have not received an anti-estrogen as part of adjuvant therapy, and they are at least 2 years from the time of their primary surgery.
- Patients must have completed all planned adjuvant therapy, including surgery, chemotherapy, and radiation therapy, at least 4 weeks prior to treatment. There is no limit as to the amount of time that may have passed since completion of adjuvant therapy and initiation of treatment.
- Patients must be postmenopausal, as defined by either:
- Patients must have a history of breast cancer confirmed by the Department of Pathology at Memorial Sloan-Kettering Cancer Center.
- Patients must be at least 18 years old, and must be able to give written informed consent.
Key exclusion criteria (7 listed)
- Prior history of bilateral mastectomy.
- Prior history of ovarian or endometrial cancer.
- Prior or current history of osteoporosis, as defined by a lumbar-spine bone mineral density < 2.5 SD below the mean value for normal premenopausal women.
- Use of bisphosphonates or calcitonin within the past 3 months.
- Prior history of venous thrombosis or pulmonary embolism.
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 |
|---|---|---|
| Raloxifene followed by combination therapyPatients will be randomized to either Raloxifene at 60mg P.O. (each day) for 2 weeks (time designated: week- 2) After two weeks of single agent therapy, patients will be started on combination therapy with oral raloxifene (60mg/day) and oral exemestane (25mg/day) (time designated week 0), and continued on both drugs for one year (month 12). Patients will be required to start supplemental calcium (900-1500 mg/day) plus vitamin D (400-600 units/day) P.O. each day during week 0. | Drug | A |
| Exemestane followed by combination therapyPatients will be randomized to Exemestane at 25mg P.O. for 2 weeks (time designated: week- 2) After two weeks of single agent therapy, patients will be started on combination therapy with oral raloxifene (60mg/day) and oral exemestane (25mg/day) (time designated week 0), and continued on both drugs for one year (month 12). Patients will be required to start supplemental calcium (900-1500 mg/day) plus vitamin D (400-600 units/day) P.O. each day during week 0. | Drug | B |
Primary outcome
To evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a hx of AJCC Stage 0, I, II, or III breast cancer, who have no clinical evidence of disease, after completion of all planned adjuvant
Time frame: 1 year
1 secondary outcome
To determine the feasibility of using mammography and breast MRI imaging to assess the effects of raloxifene plus exemestane on radiographic breast density.
Time frame: baseline and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2023.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
Maura Dickler, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Raloxifene followed by combination therapy and Exemestane followed by combination therapy in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center 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 11 inclusion and 7 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 5 Jul 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a hx of AJCC Stage 0, I, II, or III breast cancer, who have no clinical evidence of disease, after completion of all planned adjuvant (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jul 2023.