Cancer Clinical Trials Service - SOLE
This study is currently recruiting!
Study Title
A phase II trial evaluating the role of continuous letrozole versus intermittent letrozole following 4-6 years of prior adjuvant endocrine therapy for postmenopausal women with hormone receptor positive, node positive early stage breast cancer.
Basic Study Information
Chief Investigator: Prof Alastair Thompson (UK)
Sponsor: International Breast Cancer Studies Group (IBCSG)
Phase: III
Study Status: recruiting
Cancer Type: Breast
EUDRACT No: 2007-0013780-88
ISRCTN No: ISRCTN43286545
Ethical Approval: West of Scotland Research Ethics Service (WoSRES)
Study Brief
Questions remain about the optimal duration and best schedule of AIs in the extended adjuvant setting. This trial tests the hypothesis that introducing 3-month treatment free intervals during the course of five years of extended adjuvant letrozole will improve disease free survival. This hypothesis is based on the theoretical principal that letrozole withdrawal for 3 months will permit some estrogenic stimulation which makes residual resistant disease susceptible to letrozole reintroduction.
Study Schema
Objectives
Primary:
- Disease-free survival (DFS)
Time from randomisation to first occurrence of:- Local relapse (including invasive recurrence restricted to the breast after breast-conserving treatment)
- Regional relapse
- Distant relapse
- Contralateral breast cancer
- Appearance of a second (non-breast) malignancy
- Death from any cause
Secondary:
- Overall survival (OS)
- Distant disease-free survival (DDFS)
- Breast cancer free interval (BCFI)
- Sites of first failure
- Second (non-breast) malignancies
- Deaths without prior cancer events
- Adverse events
Eligibility Criteria
Inclusion Criteria
- Patients must be postmenopausal definitive confirmation of postmenopausal status is required
- Patients must be accessible for follow-up
- At diagnosis, patients must have had operable, non-inflammatory breast cancer
- Patients must be clinically disease-free at randomization
- Patients must have had steroid hormone receptor positive tumors (ER and/or PgR), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy
- Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes
- There must have been no evidence of recurrent disease or distant metastatic disease at any time prior to randomization
- Patients must have had proper local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease.
- Patients must have clinically adequate hepatic function
- Patients must have completed 4 to 6 years of prior adjuvant endocrine therapy with SERM(s), aromatase inhibitor(s), or a sequential combination of both. When calculating 4-6 years, neoadjuvant endocrine therapy should not be included
- Patients must have stopped prior endocrine SERM/AI therapy, and must be randomized within 12 months (1 year) of the last dose of prior endocrine SERM/AI therapy
- Patients may have received any type of prior adjuvant therapy, including but not limited to neoadjuvant chemotherapy, neoadjuvant endocrine therapy, adjuvant chemotherapy, trastuzumab, ovarian ablation, GnRH analogues, lapatinib
- Patients must have stopped hormone replacement therapy (HRT), bisphosphonates (except for treatment of bone loss), or any investigational agent at randomization
- Pathology material from the primary tumor must be available for submission for central review as part of the quality control measures for this protocol
- Written Informed Consent (IC) must be signed and dated by the patient and the investigator prior to randomization
- Written consent to pathology material submission, indicating the patient has been informed of and agrees to tissue material use, transfer and handling, must be signed and dated by the patient and the investigator prior to randomization.
Exclusion Criteria
- Patients who have had bilateral breast cancer
- Patients who have had a bone fracture due to osteoporosis at any time during the 4-6 years of prior endocrine SERM/AI therapy
- Patients who have had any previous or concomitant malignancy EXCEPT adequately treated: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, contra- or ipsilateral in situ breast carcinoma
- Patients who have had any other non-malignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up
- Patients with psychiatric, addictive, or any disorder which compromises compliance with protocol requirements.
Recruitment
Target Recruitment: 300 (UK), 4800 (worldwide)
Current Recruitment: 74 : April 2011 (UK), 2376: March 2011(worldwide)
Key Dates
Accrual Opening date: Jul 2010 (UK)
Planned Accrual Completion date: Dec 2012
Planned Study Completion date: Dec 2022
Registration Information
Centre accesses IBCSG Randomisation System from the IBCSG website (www.ibcsg.org)
Main Contact
Principal Trial Coordinator: Tracy McEleney
Tel: 0131 275 6544
Fax: 0131 275 7512
Email: tmceleney@nhs.net
