An open label, randomised multicentre comparative trial of five years adjuvant exemestane treatment versus adjuvant tamoxifen followed by exemestane in postmenopausal women with early breast cancer
| ISRCTN | ISRCTN75225940 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN75225940 |
| EudraCT/CTIS number | 2004-002080-24 |
| ClinicalTrials.gov number | NCT00032136 |
| Secondary identifying numbers | N/A |
- Submission date
- 01/07/2001
- Registration date
- 01/07/2001
- Last edited
- 29/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Doctors often use hormone therapy to treat early breast cancer in postmenopausal women. Tamoxifen is a type of hormone therapy. We knew from research that taking tamoxifen for 5 years lowered the risk of breast cancer coming back. We also knew that other types of hormone therapy may also reduce the risk of breast cancer coming back. In this study we are looking at a drug called exemestane. We are comparing tamoxifen and exemestane as treatment for breast cancer in women who have been through the menopause. The aim of the trial is to find out if taking exemestane for 5 years is better than taking tamoxifen for 2-3 years before switching to exemestane.
Who can participate?
Women with breast cancer who have been through the menopause.
What does the study involve?
Patients will be randomly allocated to either have exemestane for 5 years, or tamoxifen for 2.5 years followed by exemestane for 2.5 years. Patients will attend follow-up clinics regularly for the duration of the study.
What are the possible benefits and risks of participating?
Tamoxifen is a drug taken orally once a day, which prevents the natural hormone oestrogen from encouraging breast cancer cells to grow by blocking the effects of oestrogen in cells. When taken after surgery for breast cancer we know that it reduces the risk of a breast cancer recurrence. Breast cancer recurrence can happen near the original cancer (local relapse) or at distant sites such as bones or liver (distant relapse). Tamoxifen reduces the risk of this happening. We know that tamoxifen should be taken for at least 5 years to gain maximum benefit. Tamoxifen is a very valuable treatment and is saving many lives when used after breast cancer surgery. Tamoxifen given for 5 years after surgery remains an appropriate treatment for many women with oestrogen receptor-positive breast cancer and is an effective way to reduce, but not eliminate, the risk of recurrence. Tamoxifen can cause a very long list of side effects but the most common side effects are menopausal-type hot flushes. Tamoxifen also helps maintain bone strength. Although some women experience vaginal discharge or even vaginal bleeding, this is uncommon and you should always tell your doctor if this happens. Tamoxifen increases the risk of developing cancer of the womb lining (endometrial cancer). Tamoxifen also increases the risk of blood clots in the legs (deep vein thrombosis) and blood clots on the lung (pulmonary embolus). These increased risks are very small and are greatly outweighed by the benefits of taking tamoxifen.
Exemestane is a new drug that until very recently has been used only for the treatment of breast cancer after tamoxifen has stopped working in patients with relapsed or advanced breast cancer. New trial information now shows that if we introduce exemestane after 2 or 3 years of tamoxifen this reduces the risk of breast cancer recurrence. We do not yet know about the long-term effects of this combination on chances of survival but since the treatment reduces the risk of breast cancer recurrence by about a third many doctors now think this sequential treatment is the right treatment for some patients with early breast cancer. Exemestane has now been compared to tamoxifen as treatment for advanced breast cancer and is slightly more effective than tamoxifen. We now want to study how well exemestane works when given as an adjuvant therapy immediately after surgery rather than after a period of time on tamoxifen. Exemestane works by preventing the formation of oestrogen. It only works in women who have gone through the change and are no longer having menstrual periods (postmenopausal women). Exemestane is taken orally, once per day. Exemestane also has a long list of possible side effects including hot flushes, nausea and fatigue. For most people these side effects are mild. We do not know if exemestane is a better hormone treatment to use after surgery and the TEAM study is designed to find out if exemestane is better than tamoxifen or not.
Where is the study run from?
The study is run by the Cancer Research UK Clinical Trial Unit (CRCTU) at the University of Birmingham (UK).
When is the study starting and how long is it expected to run for?
The study started recruitment in 2001 and finished recruitment in 2005.
Who is funding the study?
Funding has been provided by Pfizer through an educational grant.
Who is the main contact?
Claire Gaunt
team@trials.bham.ac.uk
Contact information
Scientific
Cancer Research UK Clinical Trials Unit
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| Phone | +44(0) 121 414 3797 |
|---|---|
| team@trials.bham.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | An open label, randomised multicentre comparative trial of five years adjuvant exemestane treatment versus adjuvant tamoxifen followed by exemestane in postmenopausal women with early breast cancer |
| Study acronym | TEAM - Tamoxifen and Exemestane Adjuvant Multicentre trial |
| Study objectives | To compare the efficacy and tolerability of exemestane versus tamoxifen followed by exemestane given in the adjuvant setting in postmenopausal women with Estrogen Receptor (ER) and/or Progesterone Receptor (PgR)-positive early breast cancer. |
| Ethics approval(s) | West Midlands Multi-centre Research Ethics Committee, 31/07/2001, REC ref: MREC/01/7/26 |
| Health condition(s) or problem(s) studied | Breast cancer |
| Intervention | 1. Tamoxifen 20 mg/day for 2.5-3 years then Exemestane 25 mg/day to complete five years 2. Exemestane 25 mg/day for five years |
| Intervention type | Other |
| Primary outcome measure | Relapse Free Survival (RFS) |
| Secondary outcome measures | 1. Overall Survival (OS) 2. Incidence of contralateral breast cancer 3. Safety and long-term tolerability of both hormonal regimens |
| Overall study start date | 01/12/2001 |
| Completion date | 27/04/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 1275 in UK and Ireland |
| Key inclusion criteria | 1. Women with histologically/cytologically confirmed early adenocarcinoma of the breast, completely excised by surgery with curative intent (Ro) including: 1.1. Any node-positive cancer 1.2. Any cancer greater than or equal to 3 cm 1.3. Node negative cancer, grade II or III and 1 cm or greater 2. ER and/or PgR status positive 3. Postmenopausal 4. Patients on Hormone Replacement Therapy (HRT) which was discontinued at least four weeks prior to randomisation 5. Adequate haematological, renal and hepatic function 6. Accessible for follow-up for the duration of the trial 7. Eastern Cooperative Oncology Group (ECOG) performance status zero, one or two 8. Written informed consent (according to International Conference on Harmonisation [ICH]/Good Clinical Practice [GCP] and local Institutional Review Board [IRB] guidelines) 9. Randomisation within ten weeks of completing surgery +/- adjuvant chemotherapy |
| Key exclusion criteria | 1. Positive supraclavicular nodes 2. Evidence of distant metastases (M1) 3. Patients whose chemotherapy was started more than ten weeks after completion of primary surgery 4. Patients who have received previous hormonal treatment as adjuvant treatment for breast cancer 5. Patients who have received neoadjuvant chemotherapy 6. Neoadjuvant hormone therapy more than four weeks duration prior to surgery 7. Severe osteoporosis (bisphosphonates for therapeutic use is not an exclusion criterion) 8. Uncontrolled cardiac disease including unstable angina, Congestive Heart Failure (CHF) or arrhythmia requiring medical therapy or with a history of myocardial infarction within the past 3 months or any other serious concomitant disease 9. Psychiatric disorders preventing proper informed consent 10. Concomitant malignancies except for adequately treated carcinoma in situ of the uterine cervix or basal cell carcinoma of the skin 11. Patients with other malignancies must be disease free for at least five years 12. Concurrent participation in another clinical study (with the exception of adjuvant cytotoxic chemotherapy trials) involving investigational agents that may interfere with the results of the trial 13. Other serious illnesses that may interfere with subject compliance, adequate informed consent or determination of causality of adverse events 14. Patients on HRT, which was not discontinued at least four weeks prior to randomisation 15. Node-negative, grade I cancer less than 3 cm |
| Date of first enrolment | 01/12/2001 |
| Date of final enrolment | 07/10/2005 |
Locations
Countries of recruitment
- England
- Ireland
- United Kingdom
Study participating centre
B15 2TT
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 22/01/2011 | Yes | No |
Editorial Notes
29/04/2019: The following changes were made:
1. The recruitment end date was updated from 31/10/2005 to 07/10/2005.
2. The overall trial end date was updated from 31/10/2005 to 27/04/2018.
