Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000025437
Ethics application status
Approved
Date submitted
1/06/1996
Date registered
1/06/1996
Date last updated
11/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
IBCSG 15-95 - Randomised 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-fluoruracil x 3 as adjuvant treatment for high risk operable stage II and stage III breast cancer in premenopausal and young postmenopausal (<=65 yrs) patients
Scientific title
Randomised 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-fluoruracil x 3 as adjuvant treatment for high risk operable stage II and stage III breast cancer in premenopausal and young postmenopausal (<=65 yrs) patients
Secondary ID [1] 13 0
National Clinical Trials Registry: NCTR130
Universal Trial Number (UTN)
Trial acronym
IBCSG Trial 15-95
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 13 0
Condition category
Condition code
Cancer 13 13 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm B: Filgrastim (10ug/kg subcutaneously daily) for 6 days with leukapheresis on days 5-7. This is followed by 3 cycles (cycle =21 days) Epirubicin (200mg/m^2 iv over 12 hours on day 1), cyclophosphamide (4gm/m^2 iv as 4 divided doses – day 2), MESNA (7.2gm/m^2 – days 2 & 3), Peripheral Blood Progenitor Cell (PBPC) infusion (day 5) and Filgrastim (5ug/kg daily subcutaneously – from day 6 until White Blood Cells>10 x 10^9/l). Tamoxifen (20mg orally daily) then follows for 5 years.
Intervention code [1] 1287 0
Treatment: Drugs
Comparator / control treatment
Arm A: On day 1 of 4 cycles (cycle = 21 days) Epirubicin (90mg/m^2 iv) or Doxorubicin ( 60mg/m^2 iv) in combination with cyclophosphamide (600mg/m^2 iv) followed by 3 cycles (cycle = 28 days) cyclophosphamide (100mg/m^2 orally days 1-14), methotrexate (40mg/m^2 iv days 1 & 8) and 5-Fluorouracil (600mg/m^2 iv days 1 & 8) and then Tamoxifen (orally 20mg - daily) for 5 years.
Control group
Active

Outcomes
Primary outcome [1] 25 0
Overall survival
Timepoint [1] 25 0
Followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.
Primary outcome [2] 26 0
Duration quality-adjusted time without symptoms and toxicity (TWiST and Q-TWiST)
Timepoint [2] 26 0
Followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.
Secondary outcome [1] 40 0
Disease-free survival and Systemic disease-free survival duration.
Timepoint [1] 40 0
These secondary outcomes are followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.
Secondary outcome [2] 41 0
Toxicity
Timepoint [2] 41 0
These secondary outcomes are followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.
Secondary outcome [3] 42 0
Quality of life
Timepoint [3] 42 0
These secondary outcomes are followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.
Secondary outcome [4] 43 0
Cost-effectiveness
Timepoint [4] 43 0
These secondary outcomes are followed 3 monthly during years 1 – 2, 6 monthly during years 3-5 and then annually until death.

Eligibility
Key inclusion criteria
• Histologically proven breast cancer• Primary tumour must be classified as T1a,b,c, T2 or T3, N1 or N2, M0• Patients must be categorized as at least one of the following:a) >/= 10 involved axillary nodesb) >/= 5 involved axillary nodes and primary tumour that is ER-negativec) >/= 5 involved axillary nodes and T3 tumour who had breast cancer surgical procedure (irrespective of ER status)• Attempts should be made to determine estrogen receptor status of tumour• Patients must have had:a) Either total mastectomy or breast-conserving procedure (lumpectomy or quadrantectomy) for T1, T2 or T3 tumours.b) Primary breast cancer surgical procedure must be within six weeks prior to randomization• Tumour must be confined to breast and axillary lymph nodes. All nodes must be examined by pathologist• Left ventricular ejection fraction greater than 50% by resting MUGA radionuclide scan• Adequate marrow function (WBC >/= 4.0 x 10^9/l and platelet count >/= 100 x 10^9/l)• Adequate renal function (serum creatinine </= 120 mmol/l) and hepatic function (bilirubin </= 20 umol/l, AST (SGOT) </= 2 times the upper limit of normal)• Informed consent• Geographically accessible for follow-up• ECOG performance status 0-2.
Minimum age
16 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Malignant tumours other than carcinoma• Locally inoperable breast cancer as defined by following:a) satellite skin nodules distant to primary tumourb) supraclavicular node involvementc) inoperable, matted axillary nodesd) primary tumour fixed to the chest wall, excluding pectoralis major• Distant metastases• Bilateral malignancies, or mass in opposite breast• Other malignancies except basal cell carcinoma or carcinoma in situ of cervix• Non-malignant disease preventing treatment options or prolonged follow-up• Prior therapy for breast cancer• Pregnant or lactating women• Psychiatric, addictive or any disorder preventing informed consent• Bone scan showing hot spots which cannot be confirmed as benign disease.

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)
Central randomisation by phone or fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated stratified blocks
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/1995
Actual
25/10/1995
Date of last participant enrolment
Anticipated
Actual
1/03/2000
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
344
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 15 0
Self funded/Unfunded
Name [1] 15 0
Australia and New Zealand Breast Cancer Trials Group
Country [1] 15 0
Australia
Primary sponsor type
Other Collaborative groups
Name
International Breast Cancer Study Group
Address
Effingerstrasse 40, 3008 Bern
Country
Switzerland
Secondary sponsor category [1] 13 0
Other Collaborative groups
Name [1] 13 0
Australia and New Zealand Breast Cancer Trials Group
Address [1] 13 0
PO BOX 155
HRMC NSW 2310
Country [1] 13 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 154 0
Canberra Hospital
Ethics committee address [1] 154 0
Ethics committee country [1] 154 0
Australia
Date submitted for ethics approval [1] 154 0
Approval date [1] 154 0
Ethics approval number [1] 154 0
Ethics committee name [2] 155 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [2] 155 0
Ethics committee country [2] 155 0
Australia
Date submitted for ethics approval [2] 155 0
Approval date [2] 155 0
Ethics approval number [2] 155 0
Ethics committee name [3] 156 0
Prince of Wales Hospital
Ethics committee address [3] 156 0
Ethics committee country [3] 156 0
Australia
Date submitted for ethics approval [3] 156 0
Approval date [3] 156 0
Ethics approval number [3] 156 0
Ethics committee name [4] 157 0
Royal North Shore Hospita
Ethics committee address [4] 157 0
Ethics committee country [4] 157 0
Australia
Date submitted for ethics approval [4] 157 0
Approval date [4] 157 0
Ethics approval number [4] 157 0
Ethics committee name [5] 158 0
Royal Prince Alfred Hospital
Ethics committee address [5] 158 0
Ethics committee country [5] 158 0
Australia
Date submitted for ethics approval [5] 158 0
Approval date [5] 158 0
Ethics approval number [5] 158 0
Ethics committee name [6] 159 0
Mater Hospital, Brisbane
Ethics committee address [6] 159 0
Ethics committee country [6] 159 0
Australia
Date submitted for ethics approval [6] 159 0
Approval date [6] 159 0
Ethics approval number [6] 159 0
Ethics committee name [7] 160 0
Royal Brisbane and Women's Hospital
Ethics committee address [7] 160 0
Ethics committee country [7] 160 0
Australia
Date submitted for ethics approval [7] 160 0
Approval date [7] 160 0
Ethics approval number [7] 160 0
Ethics committee name [8] 161 0
Queen Elizabeth Hospital
Ethics committee address [8] 161 0
Ethics committee country [8] 161 0
Australia
Date submitted for ethics approval [8] 161 0
Approval date [8] 161 0
Ethics approval number [8] 161 0
Ethics committee name [9] 162 0
Royal Adelaide Hospital
Ethics committee address [9] 162 0
Ethics committee country [9] 162 0
Australia
Date submitted for ethics approval [9] 162 0
Approval date [9] 162 0
Ethics approval number [9] 162 0
Ethics committee name [10] 163 0
Alfred Hospital
Ethics committee address [10] 163 0
Ethics committee country [10] 163 0
Australia
Date submitted for ethics approval [10] 163 0
Approval date [10] 163 0
Ethics approval number [10] 163 0
Ethics committee name [11] 164 0
Austin Health
Ethics committee address [11] 164 0
Ethics committee country [11] 164 0
Australia
Date submitted for ethics approval [11] 164 0
Approval date [11] 164 0
Ethics approval number [11] 164 0
Ethics committee name [12] 165 0
Bendigo Hospital
Ethics committee address [12] 165 0
Ethics committee country [12] 165 0
Australia
Date submitted for ethics approval [12] 165 0
Approval date [12] 165 0
Ethics approval number [12] 165 0
Ethics committee name [13] 166 0
Box Hill Hospital
Ethics committee address [13] 166 0
Ethics committee country [13] 166 0
Australia
Date submitted for ethics approval [13] 166 0
Approval date [13] 166 0
Ethics approval number [13] 166 0
Ethics committee name [14] 167 0
Monash Medical Centre
Ethics committee address [14] 167 0
Ethics committee country [14] 167 0
Australia
Date submitted for ethics approval [14] 167 0
Approval date [14] 167 0
Ethics approval number [14] 167 0
Ethics committee name [15] 168 0
Peter MacCallum Cancer Centre
Ethics committee address [15] 168 0
Ethics committee country [15] 168 0
Australia
Date submitted for ethics approval [15] 168 0
Approval date [15] 168 0
Ethics approval number [15] 168 0
Ethics committee name [16] 169 0
Royal Melbourne Hospital
Ethics committee address [16] 169 0
Ethics committee country [16] 169 0
Australia
Date submitted for ethics approval [16] 169 0
Approval date [16] 169 0
01/07/1995
Ethics approval number [16] 169 0
Ethics committee name [17] 170 0
St Vincent's Hospital, Melbourne
Ethics committee address [17] 170 0
Ethics committee country [17] 170 0
Australia
Date submitted for ethics approval [17] 170 0
Approval date [17] 170 0
Ethics approval number [17] 170 0
Ethics committee name [18] 171 0
Western Hospital
Ethics committee address [18] 171 0
Ethics committee country [18] 171 0
Australia
Date submitted for ethics approval [18] 171 0
Approval date [18] 171 0
Ethics approval number [18] 171 0
Ethics committee name [19] 172 0
Sir Charles Gairdner Hospital
Ethics committee address [19] 172 0
Ethics committee country [19] 172 0
Australia
Date submitted for ethics approval [19] 172 0
Approval date [19] 172 0
Ethics approval number [19] 172 0
Ethics committee name [20] 173 0
Auckland Hospital
Ethics committee address [20] 173 0
Ethics committee country [20] 173 0
New Zealand
Date submitted for ethics approval [20] 173 0
Approval date [20] 173 0
Ethics approval number [20] 173 0

Summary
Brief summary
This clinical trial is for premenopausal and young postmenopausal women who after their breast cancer surgery have been found to have cancer cells in the glands of the armpit (‘positive axillary lymph nodes’) and whose tumours do not have oestrogen receptors (are not stimulated by oestrogen). These tumour characteristics are often associated with a higher risk for breast cancer recurrence.

It is known that chemotherapy in standard doses after breast cancer surgery reduces the chance of breast cancer recurrence. However, this clinical trial aims to assess whether giving higher doses of chemotherapy is more effective in killing remaining cancer cells in women with a high risk of recurrence. Women will be allocated randomly (like the toss of a coin) to have either standard chemotherapy for their breast cancer, or high dose chemotherapy.
Trial website
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 35818 0
Prof John F Forbes
Address 35818 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 35818 0
Australia
Phone 35818 0
+61 2 4985 0113
Fax 35818 0
Email 35818 0
[email protected]
Contact person for public queries
Name 10476 0
Ms Corinna Beckmore
Address 10476 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 10476 0
Australia
Phone 10476 0
+61 2 4925 3068
Fax 10476 0
+61 2 4985 0141
Email 10476 0
[email protected]
Contact person for scientific queries
Name 1404 0
Prof John F Forbes
Address 1404 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 1404 0
Australia
Phone 1404 0
+ 61 2 4985 0113
Fax 1404 0
+ 61 2 4960 1539
Email 1404 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.