Condition category
Cancer
Date applied
20/09/2005
Date assigned
12/10/2005
Last edited
24/09/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

https://www.lotus-f.net/portal

Contact information

Type

Scientific

Primary contact

Dr Prasert Lertsaguansinchai

ORCID ID

Contact details

Department of Radiology
Wongwanich Building
Chulalongkorn University Hospital
Rama IV Street
Pratumwam
Bangkok
10330
Thailand
+66 22564590, 91203311, 4736842
Prasert@chularcancer.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CFEM345DTH01

Study information

Scientific title

Acronym

LOTUS trial

Study hypothesis

Letrozole is more effective than tamoxifen in first line treatment of metastatic breast cancer.
In advanced disease, letrozole has been associated with significantly more tumor regression than anastrozole, especially in patients with unknown ER status. Letrozole has also been shown to be more effective than tamoxifen in the neoadjuvant treatment of breast cancer. Recently, anastrozole has been shown to induce a reduction in the rate of relapse as compared with tamoxifen in the adjuvant setting. Extended adjuvant therapy with letrozole after 5 years tamoxifen has been demonstrated to reduce the risk of recurrence and to improve significantly the disease–free survival of postmenopausal women with early breast cancer. International studies are investigating the effect of letrozole compared to tamoxifen in the adjuvant treatment of early breast cancer patients. Few Asian patients are included. A large number of early breast cancer patients in Thailand are currently being treated with tamoxifen as adjuvant treatment.
It is not yet clear whether aromatase inhibitor can replace tamoxifen as adjuvant treatment for early breast cancer. Sequence and timing of tamoxifen and aromatase inhibitor treatment in adjuvant treatment still needs to be determined as well.
The goals of this study are the following:
1. To determine whether the replacement, as adjuvant therapy, of tamoxifen by letrozole for the last 3 years of a standard 5 year treatment period can reduce the risk of treatment failure in early breast cancer patients
2. To conduct this study in a Thai population
3. To compare the 2 treatments in terms of safety and tolerability

Approximately 1000 patients from up to 15 centers across Thailand will be enrolled into this study. The patient population will include postmenopausal women with resected Stage I, II, or IIIa, ER+ and/or PR+ breast cancer who have received 2 years of adjuvant tamoxifen and who have no clinical or radiological evidence of recurrent or metastatic disease before randomization. Pre-menopausal women who are/become amenorrheic due to either chemotherapy or Luteinizing Hormone Releasing Hormone (LHRH) use may participate in the study. Patients must have undergone complete tumor resection and margins of the resected specimen must be microscopically free of tumor.

Ethics approval

Not provided at time of registration

Study design

Open-label, Randomized Study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

ER positive and/or PR positive early breast cancer

Intervention

After providing consent, patients will be screened for eligibility.
Eligible patients will be registered at any time up to 2 years (+/- 3 months) of tamoxifen treatment. Tamoxifen treatment had to be started at a dose of 20 mg/day for 2 years. After that, patients event-free will be randomly assigned to continue receiving tamoxifen for an additional 3 years or receiving letrozole 2.5 mg/day for 3 years.
After completion of treatment, patients should be followed up for study end points for 3 years.

Intervention type

Drug

Phase

Not Specified

Drug names

Letrozole, tamoxifen

Primary outcome measures

Compare these treatment regimens in terms of disease free survival (DFS)

Secondary outcome measures

1. Compare these treatment regimens in terms of overall survival (OS)
2. Compare these treatment regimens in terms of safety and tolerability in the Thai patient population

Overall trial start date

01/01/2005

Overall trial end date

31/12/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with stage I, II or IIIa adenocarcinoma of the breast at diagnosis. Patients with breast cancer whose tumor has been completely removed macroscopically and margins of the resected tumor have been microscopically free of tumor. If appropriate, additional local (e.g. radiotherapy) and/or systemic (i.e. adjuvant chemotherapy) treatments are allowed.
2. Postmenopausal status defined by one of the following:
a. Age ≥55 years with cessation of menses
b. Age <55 but no spontaneous menses for at least 1 year
c. Age <55 and spontaneous menses within the past 1 year, but currently amenorrheic (e.g. spontaneous, or secondary to hysterectomy), and with postmenopausal gonadotrophin levels (luteinizing hormone and follicle stimulating hormone levels >40 IU/l) or postmenopausal estradiol levels (<5 ng/dl) or according to the definition of 'postmenopausal range' for the laboratory involved
d. Bilateral oophorectomy
3. Patients whose tumors are either ER+ and/or PR+ (defined as ER and/or PR ≥10 fmol/mg cytosol protein; or ≥10% of the tumor cells positive by immunohistochemical evaluation)
4. Under tamoxifen therapy for 2 years before randomization
5. At randomization, patients must have no clinical or radiological evidence of distant metastasis, and no other concomitant malignancy (confirmed by mammography, chest X-ray or computed tomography [CT] scan, bone scan and liver US)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0–2
7. No prior treatment with letrozole
8. Patients must be accessible for follow-up
9. Signed written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1000

Participant exclusion criteria

1. Patients with any clinical or radiological evidence of distant spread of their disease at any point before randomization
2. Patients with other non-malignant systemic diseases including uncontrolled infections, uncontrolled type 2 diabetes mellitus, 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 human immunodeficiency virus (HIV) are excluded.
3. Total serum calcium >2.75 mmol/l (11.0 mg/dl)
4. White Blood Cell Count (WBC) <3.0 x 10^9/l or granulocytes <1.5 x 10^9/l, platelets <100 x 10^9/l
5. Aspartate amino transferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine amino transferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >3 upper limit of normal (ULN) in combination with other laboratory and clinical abnormalities indicating liver insufficiency to a degree that precludes dosing with letrozole (Child-Pugh grade C)
6. Patients with abnormal renal function as defined by a serum creatinine ≥3 mg/dl (265.2 mmol/l)
7. Previous history of fracture within 2 years
8. Patients treated with other systemic investigational drug(s) and/or device(s) within the past 30 days
9. History of non-compliance to medical regimens and patients who are considered potentially unreliable
10. Mental illness that precludes the patient from giving informed consent

Recruitment start date

01/01/2005

Recruitment end date

31/12/2012

Locations

Countries of recruitment

Thailand

Trial participating centre

Department of Radiology
Bangkok
10330
Thailand

Sponsor information

Organisation

Thai Breast Cancer Study Group (Thailand)

Sponsor details

Department of Radiation Oncology
Chulalongkorn University Hospital
Rama 4 Street. Pratumwan
Bangkok
10330
Thailand
+66 22564590, 91203311, 4736842
Prasert@chularcancer.net

Sponsor type

Other

Website

http://www.chulacancer.net

Funders

Funder type

Industry

Funder name

Partially sponsored by Novartis Thailand

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes