Clinical trial NCT00002777: Exemestane Compared With Tamoxifen in Treating Women With Locally Recurrent or Metastatic Breast Cancer
Official title: RANDOMIZED PHASE II STUDY IN FIRST LINE HORMONAL TREATMENT FOR METASTATIC BREAST CANCER WITH EXEMESTANE OR TAMOXIFEN IN POSTMENOPAUSAL PATIENTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-04-11
Enrollment: 342
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Bankstown
country: Australia
facility: Bankstown - Lidcombe Hospital
city: Antwerp
country: Belgium
facility: Algemeen Ziekenhuis Middelheim
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Brussels (Bruxelles)
country: Belgium
facility: Centre Hospitalier Etterbeek Ixelles
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: La Louviere
country: Belgium
facility: Centre Hospitalier Universitaire de Tivoli
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Kuala Lumpur
country: Malaysia
facility: University of Malaysia Medical Center
city: 's-Gravenhage (Den Haag, The Hague)
country: Netherlands
facility: Leyenburg Ziekenhuis
city: Amersfont
country: Netherlands
facility: Ziekenhuis Eemland de Lichtenberg
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekhuis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Leidschendam
country: Netherlands
facility: Medisch Centrum Haaglanden Locatle Antoniushove
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Purmerend
country: Netherlands
facility: Waterlandziekenhuis
city: Roermond
country: Netherlands
facility: Saint Laurentius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Rotterdam Cancer Institute
city: Sittard
country: Netherlands
facility: Maasland Hospital
city: Tilburg
country: Netherlands
facility: St. Elisabeth Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis Utrecht
city: Veldhoven
country: Netherlands
facility: Sint Joseph Ziekenhuis
city: Cebu City
country: Philippines
facility: Chong Hua Medical Arts Center
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Cancer Research Center
city: Saint Petersburg
country: Russian Federation
facility: Petrov Research Institute of Oncology
city: Ljubljana
country: Slovenia
facility: Institute of Oncology, Ljubljana
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: London
country: United Kingdom
facility: Guy's and St. Thomas' Hospitals Trust
state: England
city: Middlesbrough, Cleveland
country: United Kingdom
facility: South Tees Hospitals NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
Study officials:
affiliation: University Hospital, Gasthuisberg
name: Robert Paridaens, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
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 Clin Oncol 22 (Suppl 14): A-515, 6s, 2004.
citation: 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.