Exemestane Compared With Tamoxifen in Treating Women With Locally Recurrent or Metastatic Breast Cancer

NCT ID: NCT00002777

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-05-31

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane or tamoxifen may fight cancer by blocking the uptake of estrogen.

PURPOSE: Randomized phase II/III trial to compare the effectiveness of exemestane with that of tamoxifen in treating postmenopausal women who have locally recurrent or metastatic breast cancer.

Detailed Description

OBJECTIVES:

• Compare the efficacy of exemestane vs tamoxifen, in terms of progression-free survival, in postmenopausal women with locally recurrent or metastatic breast cancer.
• Determine the safety profile of exemestane in these patients.
• Compare the overall survival of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. (Phase II of this study closed as of 6/14/00). Patients are stratified by participating center, prior adjuvant tamoxifen (yes vs no), prior chemotherapy for metastatic disease (yes vs no), and dominant site of metastasis (visceral with or without others vs bone only vs bone and soft tissue vs soft tissue only).

Patients are randomized to receive either oral exemestane or oral tamoxifen daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 18 months and then at least every 6 months thereafter.

PROJECTED ACCRUAL: A total of 342 patients will be accrued for this study within 4.7 years.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

exemestane

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Disease-free interval of at least 2 years since adjuvant therapy or initial surgery (if no adjuvant therapy), including most recently treated tumor in bilateral breast cancer if status unknown in one primary tumor

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Postmenopausal by 1 of the following:

• Natural menopause and more than 1 year since last menstrual period (LMP)
• Radiation-induced oophorectomy and more than 1 year since LMP
• Chemotherapy induced menopause if:

• At least 1 year since LMP (+ 1 year post-tamoxifen)
• Serum FSH and LH and plasma estradiol levels in postmenopausal range
• LHRH-induced amenorrhea
• Surgical castration

• Patients under age 56 with prior hysterectomy and 1 or both ovaries intact or tamoxifen-induced amenorrhea with at least 12 months since prior tamoxifen must have postmenopausal serum FSH and LH and plasma estradiol concentrations

Performance status:

• ECOG (WHO) 0-2

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT less than 2.5 times ULN (less than 5 times ULN with liver metastases)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No deep venous thrombosis

Other:

• No mental incapacitation
• No severe concurrent disease
• No prior or concurrent malignancy except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since chemotherapy for metastatic disease and recovered
• No more than 1 prior chemotherapy regimen for metastatic disease
• Prior adjuvant chemotherapy allowed if disease free for at least 6 months
• No concurrent chemotherapy

Endocrine therapy:

• No prior hormonal therapy for advanced disease (e.g., tamoxifen or LHRH agonists)
• Prior adjuvant tamoxifen allowed if disease free for at least 6 months
• No other concurrent hormonal therapy, including steroids

Radiotherapy:

• Recovered from toxic effects of prior radiotherapy
• Concurrent palliative radiotherapy, including whole brain irradiation, allowed

Surgery:

• See Disease Characteristics
• No prior ovariectomy for advanced disease

Other:

• No other concurrent investigational drugs
• Concurrent bisphosphonates allowed if short term (7 days) for hypercalcemia due to suspect tumor flare or if on prior bisphosphonates with bidimensionally measurable extraosseous lesion

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Paridaens, MD, PhD

Role: STUDY_CHAIR

University Hospital, Gasthuisberg

Locations

Liverpool Hospital

Liverpool, New South Wales, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Bankstown - Lidcombe Hospital

Bankstown, , Australia

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Institut Jules Bordet

Brussels (Bruxelles), , Belgium

Centre Hospitalier Etterbeek Ixelles

Brussels (Bruxelles), , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

Centre Hospitalier Universitaire de Tivoli

La Louvière, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Clinique Sainte Elisabeth

Namur, , Belgium

Algemeen Ziekenhuis Sint-Augustinus

Wilrijk, , Belgium

Institut Bergonie

Bordeaux, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre de Lutte Contre le Cancer, Georges-Francois Leclerc

Dijon, , France

Centre Leon Berard

Lyon, , France

Centre Eugene Marquis

Rennes, , France

Centre Henri Becquerel

Rouen, , France

Centre Rene Huguenin

Saint-Cloud, , France

University of Malaysia Medical Center

Kuala Lumpur, , Malaysia

Leyenburg Ziekenhuis

's-Gravenhage (Den Haag, the Hague), , Netherlands

Ziekenhuis Eemland de Lichtenberg

Amersfont, , Netherlands

Antoni van Leeuwenhoekhuis

Amsterdam, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Medisch Centrum Haaglanden Locatle Antoniushove

Leidschendam, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

University Medical Center Nijmegen

Nijmegen, , Netherlands

Waterlandziekenhuis

Purmerend, , Netherlands

Saint Laurentius Ziekenhuis

Roermond, , Netherlands

Rotterdam Cancer Institute

Rotterdam, , Netherlands

Maasland Hospital

Sittard, , Netherlands

St. Elisabeth Ziekenhuis

Tilburg, , Netherlands

Diakonessenhuis Utrecht

Utrecht, , Netherlands

Sint Joseph Ziekenhuis

Veldhoven, , Netherlands

Chong Hua Medical Arts Center

Cebu City, , Philippines

Medical University of Gdansk

Gdansk, , Poland

Russian Academy of Medical Sciences Cancer Research Center

Moscow, , Russia

Petrov Research Institute of Oncology

Saint Petersburg, , Russia

Institute of Oncology, Ljubljana

Ljubljana, , Slovenia

Tri-Service General Hospital

Taipei, , Taiwan

Siriraj Hospital

Bangkok, , Thailand

Guy's and St. Thomas' Hospitals Trust

London, England, United Kingdom

South Tees Hospitals NHS Trust

Middlesbrough, Cleveland, England, United Kingdom

Weston Park Hospital

Sheffield, England, United Kingdom

Western General Hospital

Edinburgh, Scotland, United Kingdom

Countries

Australia; Belgium; France; Malaysia; Netherlands; Philippines; Poland; Russia; Slovenia; Taiwan; Thailand; United Kingdom

References

Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T, Piccart MJ, Bogaerts J, Therasse P. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008 Oct 20;26(30):4883-90. doi: 10.1200/JCO.2007.14.4659. Epub 2008 Sep 15.

Reference Type: RESULT

PMID: 18794551 (View on PubMed)

Atalay G, Dirix L, Biganzoli L, Beex L, Nooij M, Cameron D, Lohrisch C, Cufer T, Lobelle JP, Mattiaci MR, Piccart M, Paridaens R. The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'. Ann Oncol. 2004 Feb;15(2):211-7. doi: 10.1093/annonc/mdh064.

Reference Type: RESULT

PMID: 14760111 (View on PubMed)

Paridaens R, Therasse P, Dirix L, et al.: First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts): A randomized phase III trial of the EORTC Breast group. [Abstract] J Clin Oncol 22 (Suppl 14): A-515, 6s, 2004.

Reference Type: RESULT

Paridaens R, Therasse P, Dirix L, et al.: First results of a randomized phase III trial comparing exemestane versus tamoxifen as first-line hormone therapy (HT) for postmenopausal women with metastatic breast cancer (MBC) : EORTC 10951 in collaboration with the exemestane working group and NCIC Clinical Trials Group. [Abstract] Eur J Cancer 2 (Suppl 3): A-241, 126, 2004.

Reference Type: RESULT

Other Identifiers

EORTC-10951

Identifier Type: -

Identifier Source: secondary_id

PHARMACIA-EORTC-10951

Identifier Type: -

Identifier Source: secondary_id

EORTC-10951

Identifier Type: -

Identifier Source: org_study_id