Clinical trial NCT00330317: Safety and Efficacy of Hormone Therapy With Letrozole in Postmenopausal Women With Breast Cancer
Official title: Neoadjuvant Hormone Therapy for Postmenopausal Women With HR+ Primary Breast Cancer: A Multi-center Study to Determine the Optimum Length of Treatment With Letrozole on Tumour Regression to Permit Breast Conserving Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Letrozole
Breast Conserving Surgery
NeoAdjuvant
Early Breast Cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-05-26
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the safety and efficacy of neoadjuvant hormone therapy with letrozole in postmenopausal women with estrogen- and/or progesterone-receptor positive primary breast cancer on tumour regression to permit breast conserving surgery.


Eligibility criteria: Inclusion Criteria:

1. Postmenopausal women able to comply with the protocol requirements with confirmed primary invasive breast cancer whose tumours are estrogen-and/or progesterone-receptor positive
2. Clinical stage T2 or \>T2 tumours which in the investigators' opinion would not be eligible for breast-conserving surgery. The nodal status will be evaluated by palpation and/or ultrasound.
3. Postmenopausal status defined by one of the following:

   * Women with an intact uterus AND

     * ≥ 55 years of age, OR
     * \< 55 years of age without menses for the last 5 years, OR
     * \< 55 years of age and have not had menses for at least the last 12 months (but have had menses in the last 5 years) and have postmenopausal levels of follicle-stimulating hormone.
   * Women without an intact uterus AND

     * ≥ 55 years of age, OR
     * \< 55 years of age and postmenopausal levels of follicle-stimulating hormone
   * Both ovaries removed (prior to the diagnosis of breast cancer).
4. Tumour measurable by clinical examination, mammography and ultrasound
5. Adequate bone marrow function as shown by:

   * WBC ≥ 3.5 x 10\^9/L
   * ANC ≥ 1.5 x 10\^9/L
   * Platelets ≥ LLN
   * Hb \> 10 g/dL

Exclusion Criteria:

1. Multifocal disease (cancer that starts in several different sites)
2. Patients with bilateral breast tumours.
3. Patients who are eligible for breast conserving surgery.
4. Evidence of inflammatory breast cancer or distant metastasis.
5. Simultaneous anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers, endocrine therapy (including steroids), bisphosphonate therapy and radiotherapy. NOTE: Bisphosphonate therapy for osteoporosis is NOT excluded, and can be continued. Patients who have received hormone replacement therapy will NOT be excluded if it is discontinued at least 2 weeks before starting the study.

The following additional treatments are NOT allowed during the treatment phase of the study:

* Any other anti-cancer therapy
* Hormone replacement therapy.
* Estrogen cream (including any intra-vaginal preparation).
* Steroids other than creams or inhalers.
* Megestrol acetate for the treatment of hot flushes.
* Radiation therapy.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Optimum length of treatment with letrozole (2.5 mg daily) preoperatively, on tumour measured by clinical examination and breast ultrasound
timeFrame: 12 months
Secondary outcomes:
measure: Reduction in tumour volume every 2 months throughout the study
timeFrame: 12 months
measure: Response rate in line with the Response Evaluation Criteria in Solid Tumors criteria
timeFrame: 12 months
measure: Long term (5-year) local recurrence rate
timeFrame: 5 years
measure: Safety and tolerability of the treatment prior to surgery
timeFrame: 5 years
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Novartis Investigative Site
city: Brighton
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Crewe
country: United Kingdom
facility: Novartis Investigative Site
city: Dundee
country: United Kingdom
facility: Novartis Investigative Site
city: East Sussex
country: United Kingdom
facility: Novartis Investigative Site
city: Epping
country: United Kingdom
facility: Novartis Investigative Site
city: Farnworth
country: United Kingdom
facility: Novartis Investigative Site
city: Gateshead
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Hants
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Luton
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle
country: United Kingdom
facility: Novartis Investigative Site
city: Poole
country: United Kingdom
facility: Novartis Investigative Site
city: St. Leonards on Sea
country: United Kingdom
facility: Novartis Investigative Site
city: West Smithfield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmeceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Carpenter R, Doughty JC, Cordiner C, Moss N, Gandhi A, Wilson C, Andrews C, Ellis G, Gui G, Skene AI. Optimum duration of neoadjuvant letrozole to permit breast conserving surgery. Breast Cancer Res Treat. 2014 Apr;144(3):569-76. doi: 10.1007/s10549-014-2835-8. Epub 2014 Feb 23.