Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00002784




Registration number
NCT00002784
Ethics application status
Date submitted
1/11/1999
Date registered
29/07/2004
Date last updated
4/04/2013

Titles & IDs
Public title
High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Combination Chemotherapy in Treating Women With High-Risk Breast Cancer
Scientific title
Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.
Secondary ID [1] 0 0
IBCSG-15-95
Secondary ID [2] 0 0
CDR0000064834
Universal Trial Number (UTN)
Trial acronym
15-95
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: Other - filgrastim
Treatment: Drugs - CMF regimen
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - epirubicin hydrochloride
Treatment: Drugs - fluorouracil
Treatment: Drugs - mesna
Treatment: Drugs - methotrexate
Treatment: Drugs - tamoxifen citrate
Treatment: Surgery - peripheral blood stem cell transplantation
Treatment: Other - low-LET electron therapy
Treatment: Other - low-LET photon therapy

Active comparator: Standard chemotherapy - EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization.

Experimental: Dose-intensive EC - High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization.


Treatment: Other: filgrastim
Filgrastim 10 mg/kg/d sc for 6 days after randomization.

Treatment: Drugs: CMF regimen
Cyclophosphamide 100 mg/m2 orally days 1 - 14, methotrexate 40 mg/m2 iv days 1 and 8, 5-fluorouracil 600 mg/m2 iv days 1 and 8. Repeat every 28 days.

Treatment: Drugs: cyclophosphamide
For high-dose EC arm: cyclophosphamide 4 gm/m2 iv as 4 divided doses. For standard chemotherapy arm: cyclophosphamide 600 mg/m2 iv day 1 of 21-day EC cycles, and cyclophosphamide 100 mg/m2 orally on days 1-14 of 28-day CMF cycles.

Treatment: Drugs: doxorubicin hydrochloride
Doxorubicin 60 mg/m2 iv on day 1 of 21-day cycles of AC.

Treatment: Drugs: epirubicin hydrochloride
Epirubicin 90 mg/m2 iv on day 1 of 21-day cycles of EC.

Treatment: Drugs: fluorouracil
5-fluorouracil 600 mg/m2 iv days 1 and 8 of 28-day cycles of CMF.

Treatment: Drugs: mesna
MESNA (7.2 gm/m2) on days 2 and 3 of 21-day cycles of dose-intensive EC.

Treatment: Drugs: methotrexate
Methotrexate 40 mg/m2 iv on days 1 and 8 of 28-day cycles of CMF.

Treatment: Drugs: tamoxifen citrate
Tamoxifen 20mg daily for 5 years or until relapse.

Treatment: Surgery: peripheral blood stem cell transplantation
Peripheral blood progenitor cells (PBPC) infusion on day 5 of each 21-day cycle of dose-intensive EC.

Treatment: Other: low-LET electron therapy
Radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.

Treatment: Other: low-LET photon therapy
radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-free survival.
Timepoint [1] 0 0
16 years after randomization.
Secondary outcome [1] 0 0
Overall survival.
Timepoint [1] 0 0
16 years after randomization.
Secondary outcome [2] 0 0
Toxicity.
Timepoint [2] 0 0
5 years after randomization.
Secondary outcome [3] 0 0
Quality of life.
Timepoint [3] 0 0
16 years after randomization.

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS: Histologically proven breast carcinoma in one of the following categories: 10 or more involved axillary nodes 5 or more involved axillary nodes and either: Primary tumor estrogen receptor (ER)-negative (less than 10 femtomoles per milligram of cytosol protein) T3 tumor (regardless of ER status) Total mastectomy or breast-conserving procedure (lumpectomy or quadrantectomy) required within 6 weeks prior to randomization Tumor confined to breast and axillary nodes (T1a-c, T2, or T3, N1-2, M0 by the UICC staging system) The following conditions exclude entry: Satellite skin nodules distant from the primary tumor Supraclavicular node involvement Inoperable, matted axillary nodes Fixation of primary tumor to chest wall (excluding pectoralis major) Bilateral breast cancer (any mass in opposite breast unless biopsy-proven benign) Hot spots on bone scintigram (unless confirmed to be benign) Skeletal pain of unknown cause Hormone receptor status: ER status determination preferred, but not required

PATIENT CHARACTERISTICS: Age: 16-65 Sex: Women only Menopausal status: Any status Performance status: ECOG 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.1 mg/dL (20 micromoles/L) AST no greater than twice normal Renal: Creatinine no greater than 1.3 mg/dL (120 micromoles/L) Cardiovascular: Left ventricular ejection fraction greater than 50% by MUGA Other: No second malignancy except: Basal cell carcinoma Adequately treated carcinoma in situ of the cervix No significant nonmalignant disease that would preclude participation No psychiatric or addictive disorder that would compromise informed consent or participation No pregnant or nursing women Adequate contraception strongly advised for fertile women

PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than surgery (see Disease Characteristics)
Minimum age
16 Years
Maximum age
65 Years
Sex
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
1/06/1996
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
344
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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
Queen Elizabeth Hospital - Adelaide
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
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
5011 - Adelaide
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Switzerland
State/province [1] 0 0
Bern
Country [2] 0 0
Switzerland
State/province [2] 0 0
Lausanne
Country [3] 0 0
Switzerland
State/province [3] 0 0
Lugano
Country [4] 0 0
Switzerland
State/province [4] 0 0
Saint Gallen
Country [5] 0 0
Switzerland
State/province [5] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
ETOP IBCSG Partners Foundation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Russell Basser, MD
Address 0 0
Melbourne Health
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents


Results not provided in https://clinicaltrials.gov/study/NCT00002784