PrimaryTo investigate whether 5 years of extended adjuvant treatment with letrozole results in an improved DFS compared to 2.5 years treatment in patients with early breast cancer previously treated with endocrine agents for 5 yearsSecondaryTo…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Disease free survival
Secondary outcome
• Overall survival
• Distant disease free survival
• Contralateral breast cancer
• Safety.
Background summary
There is scientific evidence that it is beneficial to start using letrozole
after having received tamoxifen for 5 years, even if tamoxifen was stopped a
considerable time ago. Whether this is also true for other adjuvant treatment
schedules like 5 years of an aromatase inhibitor or a sequence strategy with
tamoxifen is unclear. The MA.17 trial reported that letrozole was safe and well
tolerated.
Based on the above, there seems to be a good scientific rationale to
investigate whether longer duration of extended adjuvant treatment with
letrozole improves DFS compared to shorter duration in patients with early
breast cancer, who have had adjuvant endocrine treatment for 5 years and have
completed treatment for no longer than 2 years.
Sidestudy 1: Little is known about the influence of lifestyle and therapy
compliance on the development and prognosis of breast cancer. To identify any
relation between lifestyle, disease prognosis and quality of life, two
questionnaires will be answered by the patient before and during therapy.
Sidestudy 2: Multiple prognostic and predictive markers are known to assist the
clinician and patient in the decision for adjuvant endocrine therapy or
chemotherapy, based on the risk of disease recurrence. However, none of these
markers is validated in the setting extended adjuvant endocrine therapy.
Therefore, we will seek to validate these markers in our cohort, and identify
new prognostic and predictive markers for extended adjuvant therapy and disease
recurrence.
Study objective
Primary
To investigate whether 5 years of extended adjuvant treatment with letrozole
results in an improved DFS compared to 2.5 years treatment in patients with
early breast cancer previously treated with endocrine agents for 5 years
Secondary
To compare the efficacy of 2.5 vs. 5 years of extended adjuvant letrozole with
respect to
• Overall survival
• Distant disease free survival
• Contralateral breast cancer
• Safety.
Sidestudy 1: To identify any relation between lifestyle, prognosis and quality
of life.
Sidestudy 2: To identify and validate prognostic and predictive markers for
therapy response and disease recurrence after extended therapy.
Study design
• Phase III, prospective, randomized, open-label, two-arm multicenter study
• Randomization by the Central Datacenter, stratified for prior endocrine
treatment schedule, time after completion of treatment, nodal status and prior
chemotherapy
• Efficacy assessment every 6 months during the first year, annually afterwards
• Interim analysis proposed
• Data Safety Monitoring Board (DSMB).
Intervention
Letrozole treatment 2,5 or 5 years.
Study burden and risks
Adverse effects Letrozole.
Albinusdreef 2
LEIDEN 2333 ZA
NL
Albinusdreef 2
LEIDEN 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
• Postmenopausal at the time of randomization (definition: see section 2.4.)
• Histologically proven invasive breast carcinoma (stage I, II or III), adequately treated at the time of diagnosis
• ER and/or PgR positive breast cancer, defined according to local laboratory definitions
• Completed 5 year (± 3 months) adjuvant endocrine therapy with either tamoxifen for 5 years, aromatase inhibitor(s) for 5 years AIs or as a sequence of both (provided that tamoxifen was given upfront for 2-3 years)
• No evidence of breast cancer recurrence at the time of randomization
• WHO performance status 0 or 1 (see Appendix 2)
• Adjuvant endocrine treatment completed for no longer than 2 years (with a tolerance window of 3 months)
• Accessible for follow-up for the duration of the trial
• Written informed consent
Exclusion criteria
• ER and PgR negative or unknown primary tumors
• Evidence of previous or current localized or distant breast cancer recurrence
• Bilateral breast cancer and/or (preventive) bilateral mastectomy
• Untreated hyperlipidemia (total cholesterol >= 7.75 mmol/L, triglycerides >= 2.5 x ULN)
• Concurrent use of other aromatase inhibitors
• Concurrent chemotherapy
• Any use of HRT or SERMS. Patients on HRT and willing to participate in the trial will have to discontinue HRT 4 weeks prior to randomization.
Topical estrogens are DISCOURAGED during the trial.
• Previous or concomitant malignancy (other than breast cancer) within the past 5 years (exceptEXCEPT adequately treated basal or squamous cell carcinoma of the skin or CIS of the cervix). Patients with a other malignancy in their history more than 5 years ago must be disease free for 5 years. Patients with a history of breast cancer, other than the breast cancer under study are always excluded.
• Other non-malignant systemic diseases including uncontrolled infections, uncontrolled DM-II, uncontrolled thyroid dysfunction, cardiovascular, renal, hepatic, and lung diseases which would prevent prolonged follow-up. Patients with previous history of thrombosis or thromboembolism can be included only if medically suitable.
• Patients with a known history of HIV
• Severe concomitant physical or psychological diseases that might impair compliance or assessment of drug/patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG
• Uncontrolled seizure disorders associated with falls
• Patients treated with systemic investigational drug(s) and/or device(s) within the past 30 days or topical investigational drugs within the past 7 days
• History of non-compliance to medical treatment and patients considered potentially unreliable
• Mental illness that precludes the patient from giving informed consent
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-003958-16-NL |
| CCMO | NL15375.058.06 |