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

Alternate Title

Exemestane Compared With Tamoxifen in Treating Postmenopausal Women With Primary Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	Postmenopausal		ICCG-96OEXE031-C1396-BIG9702 EORTC-10967, FRE-FNCLCC-PACS02/96OEXE031, EU-20013, EU-99002, ICCG-BIG-97/02, NCT00003418

Objectives

I.  Compare, in terms of disease-free survival and overall survival, the 
sequential administration of exemestane with administration of further 
tamoxifen until 5 years of therapy is achieved in postmenopausal women with 
operable breast cancer who have already received 2-3 years of adjuvant 
tamoxifen.

II.  Compare the regimens in terms of the incidence of contralateral breast 
cancer and long term tolerability of the regimens in these patients.

III.  Determine the tolerability of each regimen in terms of endometrial 
status, bone metabolism, lipid profile, and coagulation profile in these 
patients.

IV.  Assess quality of life in these patients treated with these regimens.

Entry Criteria

Disease Characteristics:

At diagnosis:
 Histologically confirmed unilateral adenocarcinoma of the breast that was
  considered operable 
 Must have had adequate therapy for primary disease including
  chemotherapy/ovarian ablation if appropriate and local postoperative
  radiotherapy if the patient received conservative (breast preserving)
  surgery

Must have remained disease-free after therapy for primary disease

Must have been receiving tamoxifen for minimum of 2 years and maximum of 3
years 1 month with no more than 1 month break at any one time

No inflammatory breast cancer, histologically positive supraclavicular nodes,
or ulceration/infiltration or skin metastases

No evidence of local relapse or distant metastasis (on chest x-ray,
scintigraphic bone scanning and liver ultrasonography/CT scanning) at any time

Hormone receptor status:
 Estrogen receptor positive or unknown

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 See Disease Characteristics
 Prior or concurrent bisphosphonates allowed
 Adjuvant or neoadjuvant chemotherapy for primary disease allowed

Endocrine therapy:
 At least 4 weeks since prior hormone replacement therapy (oral, topical, or
  vaginal)
 Prior low-dose progestins for relief of menopausal symptoms (up to 6 months
  duration) allowed
 No concurrent progestins
 No concurrent systemic corticosteroids for a prolonged period (i.e., greater
  than 2 weeks)
 No concurrent selective estrogen receptor modulators

Radiotherapy:
 See Disease Characteristics

Surgery:
 See Disease Characteristics

Other:
 Prior participation and completion of therapy on another clinical study of
  systemic therapy (e.g., comparison of chemotherapy schedules) allowed
 No concurrent warfarin
 Concurrent treatment for other diseases allowed only when clinically
  indicated
 

Patient Characteristics:

Age:
 Postmenopausal as defined below

Sex:
 Female

Menopausal status:
 Postmenopausal as defined by:
  55 years of age and over, and amenorrhea for greater than 2 years 
   OR
  Radiation menopause (at least 3 months previously) or surgical oophorectomy
   OR
  Natural amenorrhea for at least 1 year at breast cancer diagnosis

Performance status:
 Not specified

Life expectancy:
 Not specified

Hematopoietic:
 WBC at least 4,000/mm3
 Hemoglobin normal

Hepatic:
 SGOT no greater than 2.5 times upper limit of normal (ULN)

Renal:
 Creatinine no greater than 1.5 times ULN

Cardiovascular:
 No significant cardiac disorder

Other:
 No significant skeletal or endocrine disorders
 No clinical evidence of severe osteoporosis and/or history of osteoporotic
  fracture
 No other prior malignancy except basal cell skin cancer or carcinoma in situ
  of the cervix
 No psychiatric or addictive disorders

Expected Enrollment

Approximately 4400 patients (2200 patients in each arm) will be accrued for 
this study.

Outline

This is a randomized, double blind, multicenter study.

Following 2-3 years of adjuvant treatment with tamoxifen, patients are 
randomized to receive either oral tamoxifen daily or oral exemestane daily for 
the remainder of the 5 year period in the absence of disease relapse or 
unacceptable toxicity.

Quality of life is assessed at some centers.

Patients are followed at least every 3 months for the first year of treatment, 
every 6 months for the next two years and then annually thereafter until year 
10.

Coleman RE, Banks LM, Girgis SI, et al.: Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 8 (2): 119-27, 2007.[PUBMED Abstract]

Coombes RC, Kilburn LS, Snowdon CF, et al.: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369 (9561): 559-70, 2007.[PUBMED Abstract]

Coombes RC, Paridaens R, Jassem J, et al.: First mature analysis of the Intergroup Exemestane Study. [Abstract] J Clin Oncol 24 (Suppl 18): A-LBA527, 2006.

Coombes RC, Hall E, Gibson LJ, et al.: A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350 (11): 1081-92, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

International Collaborative Cancer Group

R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci, Protocol chair		Ph: 44-20-8846-1418

European Organization for Research and Treatment of Cancer

Robert Paridaens, MD, PhD, Protocol chair		Ph: 32-16-34-6902 Email: robert.paridaens@uz.kuleuven.ac.be

Federation Nationale des Centres de Lutte Contre le Cancer

Moise Namer, MD, PhD, Protocol chair(Contact information may not be current)		Ph: 33-49-203-1000 Email: moise.namer@wanadoo.fr

Registry Information
Official Title		Randomized Double-Blind Trial in Postmenopausal Women With Primary Breast Cancer Who Have Received Adjuvant Tamoxifen for 2-3 Years, Comparing Subsequent Adjuvant Exemestane Treatment With Further Tamoxifen
Trial Start Date		1998-02-01
Registered in ClinicalTrials.gov		NCT00003418
Date Submitted to PDQ		1998-07-08
Information Last Verified		2008-03-26