Breast CancerPhase 3NCT00003771
Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer
A Phase 3 study testing therapeutic estradiol and norethindrone acetate in people with Breast Cancer and Menopausal Symptoms, run by Regional Oncologic Center at 6 sites in 5 countries.
Trial summary
RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Cancer, Menopausal Symptoms
- What is being tested?
- therapeutic estradiol and norethindrone acetate
- How many people
- 1,300 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Sep 1997to Feb 2004
- Phase
- Phase 3
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- History of stage 0-II breast cancer with no more than 4 involved axillary nodes if nodal status and number of nodes investigated is known
- No current evidence of disease
- Hormone receptor status:
- Positive, negative, or unknown
PATIENT CHARACTERISTICS:
Age:
- Not specified
Sex:
- Female
Menopausal status:
- Menopausal or perimenopausal
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- No active liver disease
Renal:
- Not specified
Cardiovascular:
- No prior or concurrent deep vein thrombosis
- No hereditary traits for deep vein thrombosis
- No prior or concurrent cerebral stroke
- No prior or concurrent coronary disease
Other:
- No prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
- No porphyria
- No other serious disease that would prevent compliance or greatly limit life expectancy
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No concurrent chemotherapy
Endocrine therapy:
- Prior hormone replacement therapy (HRT) allowed if stopped no more than 4 weeks after breast cancer diagnosis and at least 3 months prior to study
- No prior HRT initiated after breast cancer diagnosis
- No concurrent hormonal therapy for breast cancer except tamoxifen or toremifene
Radiotherapy:
- No concurrent radiotherapy
Surgery:
- Not specified
Other:
- No prior randomization into trials comparing effects of chemotherapy and bilateral oophorectomy in premenopausal women
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Sweden2 sites
Karolinska Hospital
Stockholm, S-171 76
Uppsala University Hospital
Uppsala, S-75185
Poland1 site
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, 02-781
About this study
Official title: Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer.
PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms.
Read the detailed description
OBJECTIVES:
- Evaluate the safety of hormone replacement therapy, in terms of risk of recurrence, in women with previously treated, nonrecurrent stage 0-II breast cancer.
- Compare this regimen vs non-hormonal symptomatic treatment, in terms of quality of life and risk of death, in this patient population.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified by center, prior hormone replacement therapy before diagnosis, and concurrent tamoxifen therapy. Patients are randomized to one of two treatment arms.
- Arm I: Patients receive one of the following: Women with an intact uterus whose last menstrual bleeding has occurred within 2 years receive continuous oral cyclic estradiol-norethindrone combination comprising estradiol only on days 1-12, estradiol plus norethindrone on days 13-22, and then estradiol only on days 22-28. Women with an intact uterus whose last menstrual bleeding occurred more than 2 years prior to study receive continuous daily oral estradiol-norethindrone combination. Women who have had a hysterectomy receive continuous daily oral estradiol only.
- Arm II: Patients receive one or more non-hormonal therapies (e.g., clonidine, beta blockers, psychological support, physical exercise, acupuncture).
Treatment in both arms continues for 2 years in the absence of disease progression. Patients may continue their randomized treatment regimen at the discretion of the treating physician.
Quality of life is assessed 3 times during the study and then every two years thereafter. Gynecological health is assessed at 3 months, 6 months, and one year during the study and then annually for at least 5 years. Breast cancer is assessed every 6 months for 3 years and then annually thereafter or at the discretion of the treating physician.
PROJECTED ACCRUAL: A total of 1,300 patients will be accrued for this study within 5-6 years.
- Conditions
- Breast Cancer, Menopausal Symptoms
- Being tested
- therapeutic estradiol, norethindrone acetate
- Keywords
- menopausal symptoms, stage I breast cancer, stage II breast cancer, breast cancer in situ
- Medical subject headings
- Breast Neoplasms, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic estradiolBiological
norethindrone acetateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 1997
- Study completionFeb 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 1,300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regional Oncologic Center
- Sponsor type
- University, hospital or other
- Collaborators
- Scandinavian Breast Group, ETOP IBCSG Partners Foundation, European Organisation for Research and Treatment of Cancer - EORTC
- Investigators
- Lars Holmberg, MD, PhD, Study chair, Uppsala University HospitalJonas Bergh, MD, PhD, Study chair, Karolinska InstitutetC. Rageth, MD, PD, Study chair, Breast CenterJanusz Jaskiewicz, MD, Study chair, Maria Sklodowska-Curie National Research Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003771
- Sponsor's protocol ID
- CDR0000066897
- Other IDs
- ROC-HABITS, EORTC-10992, IBCSG-17-98, SBG-HABITS, EU-98077
- Status last verified
- Jul 2001
- First submitted
- 1 Nov 1999
- Last updated
- 20 Sep 2013
- Results posted
- No
Publications
Brincat M, Muscat Baron Y, Ciantar E. Hormone replacement in women with breast cancer: the HABITS study. Endocrine. 2004 Aug;24(3):255-7. doi: 10.1385/endo:24:3:255.
PubMed 15542894Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, Jassem J, Dobaczewska D, Fjosne HE, Peralta O, Arriagada R, Holmqvist M, Maenpaa J; HABITS Study Group. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst. 2008 Apr 2;100(7):475-82. doi: 10.1093/jnci/djn058. Epub 2008 Mar 25.
PubMed 18364505Holmberg L, Anderson H; HABITS steering and data monitoring committees. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet. 2004 Feb 7;363(9407):453-5. doi: 10.1016/S0140-6736(04)15493-7.
PubMed 14962527
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
- ClinicalTrials.gov ID
- NCT00003771
- Acronym / sponsor ID
- CDR0000066897
- Conditions
- Breast Cancer, Menopausal Symptoms
- Keywords
- menopausal symptoms, stage I breast cancer, stage II breast cancer, breast cancer in situ
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,300 participants (estimated)
- Lead sponsor
- Regional Oncologic CenterUniversity, hospital or other
- Collaborators
- Scandinavian Breast Group, ETOP IBCSG Partners Foundation, European Organisation for Research and Treatment of Cancer - EORTC
- Study start
- Sep 1997
- Study completion
- Feb 2004 (actual)
- First posted
- 27 Jan 2003 (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.
RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer.
PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms.
Detailed description
OBJECTIVES:
- Evaluate the safety of hormone replacement therapy, in terms of risk of recurrence, in women with previously treated, nonrecurrent stage 0-II breast cancer.
- Compare this regimen vs non-hormonal symptomatic treatment, in terms of quality of life and risk of death, in this patient population.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified by center, prior hormone replacement therapy before diagnosis, and concurrent tamoxifen therapy. Patients are randomized to one of two treatment arms.
- Arm I: Patients receive one of the following: Women with an intact uterus whose last menstrual bleeding has occurred within 2 years receive continuous oral cyclic estradiol-norethindrone combination comprising estradiol only on days 1-12, estradiol plus norethindrone on days 13-22, and then estradiol only on days 22-28. Women with an intact uterus whose last menstrual bleeding occurred more than 2 years prior to study receive continuous daily oral estradiol-norethindrone combination. Women who have had a hysterectomy receive continuous daily oral estradiol only.
- Arm II: Patients receive one or more non-hormonal therapies (e.g., clonidine, beta blockers, psychological support, physical exercise, acupuncture).
Treatment in both arms continues for 2 years in the absence of disease progression. Patients may continue their randomized treatment regimen at the discretion of the treating physician.
Quality of life is assessed 3 times during the study and then every two years thereafter. Gynecological health is assessed at 3 months, 6 months, and one year during the study and then annually for at least 5 years. Breast cancer is assessed every 6 months for 3 years and then annually thereafter or at the discretion of the treating physician.
PROJECTED ACCRUAL: A total of 1,300 patients will be accrued for this study within 5-6 years.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 estradiol | Biological | – |
| norethindrone acetate | Drug | – |
Primary outcome
Not reported in the source record.
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 20 Sep 2013.
- Background: PubMed 15542894Brincat M, Muscat Baron Y, Ciantar E. Hormone replacement in women with breast cancer: the HABITS study. Endocrine. 2004 Aug;24(3):255-7. doi: 10.1385/endo:24:3:255.
- Results publication: PubMed 18364505Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, Jassem J, Dobaczewska D, Fjosne HE, Peralta O, Arriagada R, Holmqvist M, Maenpaa J; HABITS Study Group. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst. 2008 Apr 2;100(7):475-82. doi: 10.1093/jnci/djn058. Epub 2008 Mar 25.
- Results publication: PubMed 14962527Holmberg L, Anderson H; HABITS steering and data monitoring committees. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet. 2004 Feb 7;363(9407):453-5. doi: 10.1016/S0140-6736(04)15493-7.
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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.
Lars Holmberg, MD, PhD study chair
Uppsala University Hospital
Jonas Bergh, MD, PhD study chair
Karolinska Institutet
C. Rageth, MD, PD study chair
Breast Center
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing therapeutic estradiol and norethindrone acetate in people with Breast Cancer and Menopausal Symptoms, run by Regional Oncologic Center at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Sweden, Finland, Norway, Poland, Switzerland. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00003771, which also lists 3 linked publications.
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 20 Sep 2013.