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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00002529




Trial ID
NCT00002529
Ethics application status
Date submitted
1/11/1999
Date registered
28/07/2004
Date last updated
3/04/2013

Titles & IDs
Public title
Hormone Therapy and Chemotherapy in Treating Perimenopausal or Postmenopausal Women With Node-Positive Breast Cancer
Scientific title
Adjuvant Therapy for Post/Perimenopausal Patients With Node Positive Breast Cancer Who Are Suitable for Endocrine Therapy Alone.
Secondary ID [1] 0 0
IBCSG-12-93
Secondary ID [2] 0 0
CDR0000078385
Universal Trial Number (UTN)
Trial acronym
12-93
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - epirubicin hydrochloride
Treatment: Drugs - tamoxifen citrate
Treatment: Drugs - toremifene

Experimental: AC with concurrent tamoxifen - AC for 4 cycles with concurrent tamoxifen for 5 years

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

Experimental: Tamoxifen alone - Tamoxifen alone for 5 years.

Experimental: AC with concurrent toremifene - AC for 4 cycles with concurrent toremifene for 5 years.

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

Experimental: Toremifene alone - Toremifene alone for 5 years.


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

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

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

Treatment: Drugs: tamoxifen citrate
Tamoxifen 20 mg daily.

Treatment: Drugs: toremifene
Toremifene 60 mg daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival - Time from randomization to death.
Timepoint [1] 0 0
17 years after randomization
Secondary outcome [1] 0 0
Disease-free and systemic disease-free survival. - Time from randomization to recurrence, metastasis, appearance of a second primary tumor or death.
Timepoint [1] 0 0
17 years from randomization
Secondary outcome [2] 0 0
Quality of life - Quality of life will be assessed using QL Questionnaires of IBCSG.
Timepoint [2] 0 0
17 years from randomization
Secondary outcome [3] 0 0
Toxicity - Assessment of toxicity according to standard criteria.
Timepoint [3] 0 0
17 years after randomization

Eligibility
Key inclusion criteria
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)
Minimum age
No limit
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Newcastle Mater Misericordiae Hospital - Newcastle
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital, Sydney - Sydney
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Anti-Cancer Council of Victoria, Melbourne - Carlton South
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital, Perth - Perth
Recruitment postcode(s) [1] 0 0
NSW 2310 - Newcastle
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3053 - Carlton South
Recruitment postcode(s) [5] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
Italy
State/province [1] 0 0
Aviano
Country [2] 0 0
Italy
State/province [2] 0 0
Brescia
Country [3] 0 0
Italy
State/province [3] 0 0
Milano
Country [4] 0 0
Italy
State/province [4] 0 0
Rimini
Country [5] 0 0
Italy
State/province [5] 0 0
Rome
Country [6] 0 0
New Zealand
State/province [6] 0 0
Auckland
Country [7] 0 0
Slovenia
State/province [7] 0 0
Ljubljana
Country [8] 0 0
South Africa
State/province [8] 0 0
Cape Town
Country [9] 0 0
Sweden
State/province [9] 0 0
Gothenburg (Goteborg)
Country [10] 0 0
Switzerland
State/province [10] 0 0
Basel
Country [11] 0 0
Switzerland
State/province [11] 0 0
Bern
Country [12] 0 0
Switzerland
State/province [12] 0 0
Lausanne
Country [13] 0 0
Switzerland
State/province [13] 0 0
Neuchatel
Country [14] 0 0
Switzerland
State/province [14] 0 0
Saint Gallen
Country [15] 0 0
Switzerland
State/province [15] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
International Breast Cancer Study Group
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00002529
Trial related presentations / publications
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.
Kenne Sarenmalm E, Odén A, Ohlén 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.
Pagani O, Gelber S, Simoncini E, Castiglione-Gertsch M, Price KN, Gelber RD, Holmberg SB, Crivellari D, Collins J, Lindtner J, Thürlimann 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.
Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, Holmberg SB, Lindtner J, Snyder R, Thürlimann 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.
Keshaviah A, Dellapasqua S, Rotmensz N, Lindtner J, Crivellari D, Collins J, Colleoni M, Thürlimann 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. Epub 2007 Jan 20.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Edda Simoncini, MD
Address 0 0
Spedali Civili di Brescia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries