Hormone Therapy and Chemotherapy in Treating Perimenopausal or Postmenopausal Women With Node-Positive Breast Cancer

NCT00002529 | Completed Phase 3 DMC

• 4 other identifiers: CDR0000078385IBCSG-12-93EU-93015NCI-F93-0010
• Study Type: interventional
• Target: 452
• Locations: 7 countries
• Sites: 20

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the uptake of estrogen. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with hormone therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy during or after combination chemotherapy or hormone therapy alone in treating perimenopausal or postmenopausal women who have stage II or stage IIIA breast cancer.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from randomization to death.

  17 years after randomization

Secondary Outcomes (3)

• Disease-free and systemic disease-free survival.

  17 years from randomization

• Quality of life

  17 years from randomization

• Toxicity

  17 years after randomization

Study Arms (6)

AC with concurrent tamoxifen

EXPERIMENTAL

AC for 4 cycles with concurrent tamoxifen for 5 years

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: tamoxifen citrate

AC followed by tamoxifen

EXPERIMENTAL

AC for 4 cycles followed by tamoxifen to 5 years from randomization.

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: tamoxifen citrate

Tamoxifen alone

EXPERIMENTAL

Tamoxifen alone for 5 years.

Drug: tamoxifen citrate

AC with concurrent toremifene

EXPERIMENTAL

AC for 4 cycles with concurrent toremifene for 5 years.

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: toremifene

AC followed by toremifene

EXPERIMENTAL

AC for 4 cycles followed by toremifene to 5 years from randomization.

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: toremifene

Toremifene alone

EXPERIMENTAL

Toremifene alone for 5 years.

Drug: toremifene

Interventions

cyclophosphamide DRUG

cyclophosphamide 600 mg/m2 i.v. day 1) every 21 days

AC followed by tamoxifen; AC followed by toremifene; AC with concurrent tamoxifen; AC with concurrent toremifene

doxorubicin hydrochloride DRUG

doxorubicin 60 mg/m2 i.v. day 1) every 21 days, intravenous.

AC followed by tamoxifen; AC followed by toremifene; AC with concurrent tamoxifen; AC with concurrent toremifene

epirubicin hydrochloride DRUG

epirubicin 90 mg/m2 i.v. day 1) every 21 days, intravenous.

AC followed by tamoxifen; AC followed by toremifene; AC with concurrent tamoxifen; AC with concurrent toremifene

tamoxifen citrate DRUG

Tamoxifen 20 mg daily.

AC followed by tamoxifen; AC with concurrent tamoxifen; Tamoxifen alone

toremifene DRUG

Toremifene 60 mg daily.

AC followed by toremifene; AC with concurrent toremifene; Toremifene alone

Eligibility Criteria

• Age: Up to 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Histologically proven stage T1-3, pN1, M0 carcinoma of the breast considered suitable for adjuvant treatment with endocrine therapy alone Estrogen receptor at least 10 fmol/mg cytosol protein or positive on immunohistochemical assay Potentially curative resection within 6 weeks of entry by one of the following: Total mastectomy with negative margins Breast-conserving procedure (lumpectomy or quadrantectomy) for tumors less than 5 cm Adequate re-resection or mastectomy within 4 weeks of initial surgery required if margins are positive after initial surgery Axillary clearance (not sampling) required at surgery, with at least 1 node positive upon histopathologic examination of at least 8 nodes Suspicious manifestations of metastatic disease (e.g., hot spots on bone scan, skeletal pain of unknown cause) must be proven benign No bilateral breast cancer Any mass in contralateral breast must be proven benign by biopsy PATIENT CHARACTERISTICS: Age: 70 and under Sex: Women only Menopausal status: Peri/postmenopausal, i.e.: More than 6 months since last normal menstrual period (LNMP) with no prior hysterectomy and no hormone replacement therapy (HRT) Prior hysterectomy and no HRT and either age greater than 55 or age 55 or less with postmenopausal LH, FSH, and E2 levels On HRT and either age 50 or greater or LNMP more than 6 months prior to starting HRT Performance status: Not specified Hematopoietic: WBC greater than 4,000 Platelets greater than 100,000 Hepatic: Bilirubin less than 1.1 mg/dL (20 micromoles/L) AST less than 60 IU/L Renal: Creatinine less than 1.3 mg/dL (120 micromoles/L) Other: No nonmalignant systemic disease that would preclude protocol therapy or prolonged follow-up No psychiatric or addictive disorder that would preclude informed consent No prior or concurrent second malignancy except: Nonmelanomatous skin cancer Adequately treated in situ carcinoma of the cervix Geographically accessible for follow-up PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than potentially curative surgery (see Disease Characteristics)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (20)

Newcastle Mater Misericordiae Hospital

Newcastle, New South Wales, NSW 2310, Australia

Location

Royal Prince Alfred Hospital, Sydney

Sydney, New South Wales, 2050, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Anti-Cancer Council of Victoria, Melbourne

Carlton South, Victoria, 3053, Australia

Location

Sir Charles Gairdner Hospital, Perth

Perth, Western Australia, 6009, Australia

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Universita di Brescia

Brescia, 25124, Italy

Location

Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Ospedale Civile Rimini

Rimini, 47037, Italy

Location

Ospedale San Eugenio

Rome, 00144, Italy

Location

Auckland Adventist Hospital

Auckland, 5, New Zealand

Location

Institute of Oncology, Ljubljana

Ljubljana, Sl-1000, Slovenia

Location

Groote Schuur Hospital, Cape Town

Cape Town, 7925, South Africa

Location

Sahlgrenska University Hospital

Gothenburg (Goteborg), S-413 45, Sweden

Location

University Hospital

Basel, CH-4031, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Hopital des Cadolles, Neuchatel

Neuchâtel, 2000, Switzerland

Location

Kantonsspital - Saint Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Universitaetsspital

Zurich, CH-8091, Switzerland

Location

Related Publications (7)

• Gianni L, Gelber S, Ravaioli A, Price KN, Panzini I, Fantini M, Castiglione-Gertsch M, Pagani O, Simoncini E, Gelber RD, Coates AS, Goldhirsch A. Second non-breast primary cancer following adjuvant therapy for early breast cancer: a report from the International Breast Cancer Study Group. Eur J Cancer. 2009 Mar;45(4):561-71. doi: 10.1016/j.ejca.2008.10.011. Epub 2008 Dec 4.

  PMID: 19062268 BACKGROUND

• Kenne Sarenmalm E, Oden A, Ohlen J, Gaston-Johansson F, Holmberg SB. Changes in health-related quality of life may predict recurrent breast cancer. Eur J Oncol Nurs. 2009 Dec;13(5):323-9. doi: 10.1016/j.ejon.2009.05.002. Epub 2009 Jul 12.

  PMID: 19596212 BACKGROUND

• Pagani O, Gelber S, Simoncini E, Castiglione-Gertsch M, Price KN, Gelber RD, Holmberg SB, Crivellari D, Collins J, Lindtner J, Thurlimann B, Fey MF, Murray E, Forbes JF, Coates AS, Goldhirsch A; International Breast Cancer Study Group. Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93. Breast Cancer Res Treat. 2009 Aug;116(3):491-500. doi: 10.1007/s10549-008-0225-9. Epub 2008 Oct 25.

  PMID: 18953651 BACKGROUND

• Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, Holmberg SB, Lindtner J, Snyder R, Thurlimann B, Murray E, Viale G, Castiglione-Gertsch M, Coates AS, Goldhirsch A; International Breast Cancer Study Group. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol. 2008 Jun 20;26(18):3006-14. doi: 10.1200/JCO.2007.14.9336. Epub 2008 May 5.

  PMID: 18458044 BACKGROUND

• Keshaviah A, Dellapasqua S, Rotmensz N, Lindtner J, Crivellari D, Collins J, Colleoni M, Thurlimann B, Mendiola C, Aebi S, Price KN, Pagani O, Simoncini E, Castiglione Gertsch M, Gelber RD, Coates AS, Goldhirsch A. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol. 2007 Apr;18(4):701-8. doi: 10.1093/annonc/mdl492. Epub 2007 Jan 20.

  PMID: 17237474 BACKGROUND

• Gianni L, Panzini I, Li S, Gelber RD, Collins J, Holmberg SB, Crivellari D, Castiglione-Gertsch M, Goldhirsch A, Coates AS, Ravaioli A; International Breast Cancer Study Group (IBCSG). Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials. Cancer. 2006 Feb 1;106(3):505-13. doi: 10.1002/cncr.21651.

  PMID: 16369994 BACKGROUND

• International Breast Cancer Study Group; Pagani O, Gelber S, Price K, Zahrieh D, Gelber R, Simoncini E, Castiglione-Gertsch M, Coates AS, Goldhirsch A. Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol. 2004 Dec;15(12):1749-59. doi: 10.1093/annonc/mdh463.

  PMID: 15550579 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin; Epirubicin; Tamoxifen; Toremifene

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Stilbenes; Benzylidene Compounds; Benzene Derivatives

Study Officials

• Edda Simoncini, MD

  Spedali Civili di Brescia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: July 29, 2004
• Study Start: May 1, 1993
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: April 4, 2013

Record last verified: 2012-07

Locations

ZA (1); SE (1); CH (6); IT (5); AU (5); NZ (1); SL (1)