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

Breast Cancer Clinical Trial

Official title:

RANDOMIZED PHASE II STUDY IN FIRST LINE HORMONAL TREATMENT FOR METASTATIC BREAST CANCER WITH EXEMESTANE OR TAMOXIFEN IN POSTMENOPAUSAL PATIENTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002777
• Other study ID #: EORTC-10951
• Secondary ID: EORTC-10951PHARM
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 29, 2012
• Start date: May 1996

Study information

• Verified date: June 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• exemestane

• tamoxifen citrate

Locations

Country	Name	City	State
Australia	Bankstown - Lidcombe Hospital	Bankstown
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	Centre Hospitalier Etterbeek Ixelles	Brussels (Bruxelles)
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Hopital de Jolimont	Haine Saint Paul
Belgium	Centre Hospitalier Universitaire de Tivoli	La Louviere
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	Algemeen Ziekenhuis Sint-Augustinus	Wilrijk
France	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
Malaysia	University of Malaysia Medical Center	Kuala Lumpur
Netherlands	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
Philippines	Chong Hua Medical Arts Center	Cebu City
Poland	Medical University of Gdansk	Gdansk
Russian Federation	Russian Academy of Medical Sciences Cancer Research Center	Moscow
Russian Federation	Petrov Research Institute of Oncology	Saint Petersburg
Slovenia	Institute of Oncology, Ljubljana	Ljubljana
Taiwan	Tri-Service General Hospital	Taipei
Thailand	Siriraj Hospital	Bangkok
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Australia,  Belgium,  France,  Malaysia,  Netherlands,  Philippines,  Poland,  Russian Federation,  Slovenia,  Taiwan,  Thailand,  United Kingdom, 

References & Publications (4)

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 E — View Citation

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 Cli

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 wi

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 Organ — View Citation