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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00002777
First received: November 1, 1999
Last updated: June 29, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: exemestane
Drug: tamoxifen citrate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: RANDOMIZED PHASE II STUDY IN FIRST LINE HORMONAL TREATMENT FOR METASTATIC BREAST CANCER WITH EXEMESTANE OR TAMOXIFEN IN POSTMENOPAUSAL PATIENTS

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Estimated Enrollment: 342
Study Start Date: May 1996
Primary Completion Date: December 2002 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven adenocarcinoma of the breast that is metastatic and progressive or locally recurrent and inoperable
  • At least one bidimensionally measurable or evaluable lesion

    • Lytic bone lesions on x-ray/CT scan, surrounded by calcified bone, and at least 1 cm
    • Bidimensionally measurable extraosseous disease required for patients on bisphosphonates
    • The following are not considered evaluable:

      • Previously irradiated lesions
      • Lymphangitic spread
      • Ascites
      • Blastic bone lesions
      • Pleural effusions
  • No rapidly progressive disease for which hormonal therapy is not indicated
  • No massive visceral disease (i.e., more than one third of any organ)
  • No brain metastases
  • Hormone receptor status:

    • Estrogen receptor positive or progesterone receptor positive, defined by 1 of the following:

      • At least 10 femtomoles H3-estrogen or at least 20 femtomoles
      • H3 progesterone binding per mg of cytosol protein by DCC or sucrose density method
      • At least 0.10 femtomoles H3-estrogen or at least 0.20 femtomoles
      • H3-progesterone binding per mg of DNA by IF/EIA technique
      • Positive immunohistochemistry noted on pathology report
    • Unknown receptor status eligible provided:

      • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002777

  Hide Study Locations
Locations
Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Australia, Victoria
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Australia
Bankstown - Lidcombe Hospital
Bankstown, Australia, NSW 2200
Belgium
Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
Centre Hospitalier Etterbeek Ixelles
Brussels (Bruxelles), Belgium, B-1050
Institut Jules Bordet
Brussels (Bruxelles), Belgium, 1000
Hopital de Jolimont
Haine Saint Paul, Belgium, 7100
Centre Hospitalier Universitaire de Tivoli
La Louviere, Belgium, 7100
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Clinique Sainte Elisabeth
Namur, Belgium, 5000
Algemeen Ziekenhuis Sint-Augustinus
Wilrijk, Belgium, 2610
France
Institut Bergonie
Bordeaux, France, 33076
Centre Regional Francois Baclesse
Caen, France, 14076
Centre Jean Perrin
Clermont-Ferrand, France, 63011
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
Dijon, France, 21079
Centre Leon Berard
Lyon, France, 69373
Centre Eugene Marquis
Rennes, France, 35064
Centre Henri Becquerel
Rouen, France, 76038
Centre Rene Huguenin
Saint Cloud, France, 92211
Malaysia
University of Malaysia Medical Center
Kuala Lumpur, Malaysia, 59100
Netherlands
Leyenburg Ziekenhuis
's-Gravenhage (Den Haag, The Hague), Netherlands, 2545 CH
Ziekenhuis Eemland de Lichtenberg
Amersfont, Netherlands, 3016 CP
Antoni van Leeuwenhoekhuis
Amsterdam, Netherlands, 1066 CX
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Catharina Ziekenhuis
Eindhoven, Netherlands, 5602 ZA
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Medisch Centrum Haaglanden Locatle Antoniushove
Leidschendam, Netherlands, 2262 BA
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6202 AZ
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Waterlandziekenhuis
Purmerend, Netherlands, 1440 AG
Saint Laurentius Ziekenhuis
Roermond, Netherlands, 6043 CV
Rotterdam Cancer Institute
Rotterdam, Netherlands, 3075 EA
Maasland Hospital
Sittard, Netherlands, 6131 BK
St. Elisabeth Ziekenhuis
Tilburg, Netherlands, 5022 GC
Diakonessenhuis Utrecht
Utrecht, Netherlands, 3508 TG
Sint Joseph Ziekenhuis
Veldhoven, Netherlands, 5500 MB DB
Philippines
Chong Hua Medical Arts Center
Cebu City, Philippines, 6000
Poland
Medical University of Gdansk
Gdansk, Poland, 80-211
Russian Federation
Russian Academy of Medical Sciences Cancer Research Center
Moscow, Russian Federation, 115478
Petrov Research Institute of Oncology
Saint Petersburg, Russian Federation, 197758
Slovenia
Institute of Oncology, Ljubljana
Ljubljana, Slovenia, Sl-1000
Taiwan
Tri-Service General Hospital
Taipei, Taiwan, NEIHU- 114
Thailand
Siriraj Hospital
Bangkok, Thailand, 10700
United Kingdom
Guy's and St. Thomas' Hospitals Trust
London, England, United Kingdom, SE1 9RT
South Tees Hospitals NHS Trust
Middlesbrough, Cleveland, England, United Kingdom, TS4 3BW
Weston Park Hospital
Sheffield, England, United Kingdom, S1O 2SJ
Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Robert Paridaens, MD, PhD U.Z. Gasthuisberg
  More Information

Additional Information:
Publications:
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.
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00002777     History of Changes
Other Study ID Numbers: EORTC-10951, EORTC-10951, PHARMACIA-EORTC-10951
Study First Received: November 1, 1999
Last Updated: June 29, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Exemestane
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014