Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

Comparison of Letrozole and Tamoxifen in Treating Postmenopausal Women With Stage IIIB, Metastatic, or Recurrent Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over Pharmaceutical / Industry NOVARTIS-2026701025 CGS-20267, NCI-V98-1388

Objectives

I.  Compare the efficacy, as evaluated by time of progression, objective 
response rate, duration of response, and time to treatment failure, of 
letrozole versus tamoxifen in postmenopausal women with advanced breast cancer.

II.  Compare the tolerability and toxicity of the 2 treatment arms in this 
patient population.

III.  Determine the survival time in each of the 2 treatment arms in this 
patient population.

IV.  Summarize time to progression, objective response rate, duration of 
response, and time to treatment failure in a subset of patients receiving 
second-line therapy in the cross-over treatment period.

Entry Criteria

Disease Characteristics:

Histologically confirmed Stage IIIB locally advanced, metastatic breast cancer
or locoregional recurrence not amenable to treatment by surgery or
radiotherapy

Postmenopausal status as defined by:
 - No spontaneous menses for at least 5 years
 - Spontaneous menses within the past 5 years but amenorrheic for at least 12
   months and LH and FSH values in postmenopausal normal range
 - Bilateral oophorectomy
 - Radiation castration and amenorrheic for at least 3 months

No inflammatory breast cancer

Evidence of disease progression for previously treated metastatic disease as
defined by:
 Appearance of new lesions or existing lesions becoming larger (greater than
  25% in measurable lesions) or worse (in case of evaluable lesions) within 3
  months prior to study 

Prior hormone therapy:
 Patients with prior neoadjuvant/adjuvant antiestrogen therapy must not have
  recurrence of disease during and 12 months after completing any such therapy
 Patients who have relapsed on hormone replacement therapy must show evidence
  of progression for at least 2 months following discontinuation of therapy

Measurable or evaluable disease required except for patients with bone disease
only, who are always eligible (including patients with blastic lesions only)

No CNS metastases

No bilateral diffuse lymphangitis carcinomatosa of the lung (greater than 50%
of lung involvement)

No evidence of metastases estimated as more than a third of the liver as
defined by sonogram and/or CT scan

Hormone receptor status:
 Estrogen receptor and/or progesterone receptor positive or both unknown

Prior/Concurrent Therapy:

Biologic therapy:
 Prior immunotherapy/biologic response modifiers as (or as part of) adjuvant
  therapy allowed
 No concurrent immunotherapy/biologic response modifiers

Chemotherapy:
 No more than 1 prior systemic chemotherapy for recurrent or metastatic breast
  cancer
 Prior neoadjuvant or adjuvant chemotherapy allowed
 Prior bisphosphonate allowed 
 Concurrent bisphosphonate allowed (if not chronic or not more than 2 courses
  for hypercalcemia) except for patients with bone metastasis only who have
  progressed while on bisphosphonate 
 No concurrent biphosphonate for prevention of bone metastases  
 No other concurrent chemotherapy

Endocrine therapy:
 No prior systemic endocrine therapy for metastatic disease, locally advanced
  disease, or locoregional recurrent disease not curable by surgery or
  radiotherapy
 Prior corticosteroids as (or as part of) adjuvant therapy allowed
 No prolonged (duration of at least 2 weeks) concurrent systemic
  corticosteroids allowed except topical applications (e.g, for rash), inhaled
  sprays (e.g., for obstructive airways diseases), eye drops, or local
  injections (e.g., intraarticular)
 No concurrent endocrine therapy including steroids
 See Disease Characteristics

Radiotherapy:
 No prior radiotherapy to the sole site of cancer being evaluated (unless 3 or
  more months after such radiotherapy there is documented disease progression)
 Concurrent radiotherapy to a limited area (e.g., for painful disease) allowed
  if not to the sole site of measurable or evaluable disease

Surgery:
 No prior adrenalectomy or hypophysectomy

Other:
 At least 30 days since prior systemic investigational drugs
 At least 7 days since prior topical investigational drugs
 No concurrent investigational drug

Patient Characteristics:

Age:
 18 and over

Sex:
 Female

Performance status:
 Karnofsky 50-100%
 WHO 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Not specified

Hepatic:
 Not specified

Renal:
 Calcium less than 11.6 mg/dL

Cardiovascular:
 No uncontrolled cardiac disease, including unstable angina

Other:
 Not HIV positive
 No history of noncompliance of medical regimens 
 No other concurrent or prior malignancy except for contralateral breast
  carcinoma, cone biopsied in situ carcinoma of the cervix uteri or adequately
  treated basal or squamous cell carcinoma of the skin
 No uncontrolled diabetes mellitus

Expected Enrollment

There will be a total of 878 patients (439 per arm) accrued into this study 
over approximately 3 years.

Outline

This is a randomized, double blind, two arm, cross-over, multicenter study.

Patients are randomized to receive daily oral doses of either letrozole or 
tamoxifen.  Patients failing on first-line therapy with one drug are switched 
to treatment with the other drug.  Treatment continues as long as the patient 
achieves a complete response, partial response, or has stable disease.

Patients are followed at least every 6 months for survival.

Mouridsen H, Sun Y, Gershanovich M, et al.: Superiority of letrozole to tamoxifen in the first-line treatment of advanced breast cancer: evidence from metastatic subgroups and a test of functional ability. Oncologist 9 (5): 489-96, 2004.[PUBMED Abstract]

Mouridsen H, Gershanovich M, Sun Y, et al.: Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19 (10): 2596-606, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Novartis Pharmaceuticals Corporation

Carolyn Brady, Protocol chair		Ph: 862-778-8300