Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000529549
Ethics application status
Approved
Date submitted
12/05/1999
Date registered
12/05/1999
Date last updated
24/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Adjuvant Treatment for patients with node-positive Breast Cancer Docetaxel sequentially or in combination with Doxorubicin, followed by CMF (cyclophosphamide, methotrexate, fluorouracil) vs. Doxorubicin alone or in combination with Cyclophosphamide, followed by CMF (cyclophosphamide, methotrexate, fluorouracil).
Scientific title
An Intergroup phase III trial to evaluate the activity of docetaxel, given either sequentially or in combination with doxorubicin, followed by CMF, in comparison to doxorubicin alone or in combination with cyclophosphamide, followed by CMF, in the adjuvant treatment of node-positive breast cancer patients
Secondary ID [1] 18 0
National Clinical Trials Registry: NCTR292
Universal Trial Number (UTN)
Trial acronym
BIG-2-98, EU-20002, RP-56976-V-315
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 17 0
Condition category
Condition code
Cancer 17 17 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm A1:doxorubicin 75 mg/m² i.v. once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks)
Arm A2:doxorubicin 60 mg/m² i.v. and cyclophosphamide 600 mg/m² i.v., once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks)
Arm B: doxorubicin 75 mg/m² i.v. day once every 21 days for 3 cycles, followed by Docetaxel 100 mg/m² i.v., once every 21 days for 3 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 30 weeks)
Arm C: doxorubicin 50 mg/m² i.v. and docetaxel 75 mg/m² i.v. once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks)
Intervention code [1] 1244 0
Treatment: Drugs
Comparator / control treatment
to be confirmed
Control group
Active

Outcomes
Primary outcome [1] 32 0
To compare disease free survival of adjuvant treatment containing docetaxel, either sequentially or in combination with doxorubicin followed by CMF (Cyclophosphamide, Methotrexate, Fluoruracil) to doxorubicin alone or in combination with cyclophosphamide followed by CMF.
Timepoint [1] 32 0
The primary outocome was assessed at a median follow up of 5 years. The primary analysis was performed in March 2006.
Secondary outcome [1] 53 0
To compare disease free survival of all treatment arms.
Timepoint [1] 53 0
The secondary outocomes were assessed at a median follow up of 5 years. The primary analysis was performed in March 2006.
Secondary outcome [2] 54 0
Toxicity and overall survival of treatment arms.
Timepoint [2] 54 0
The secondary outocomes were assessed at a median follow up of 5 years. The primary analysis was performed in March 2006.

Eligibility
Key inclusion criteria
Written or witnessed informed consent. Histologically proven breast cancer. Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection. Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin. Histologic examination of the tumor: invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of eight resected lymph nodes. The determination of ER (estrogen receptor) and PgR (progesterone receptor) is mandatory. Karnofsky Performance status index > or equal to 70 %. Normal cardiac function must be confirmed by assessment of LVEF (MUGA scan or echocardiography). Laboratory requirements: (within 14 days prior to registration) a) Hematology: i) Neutrophils > or equal to 2.0 x 109/Lii) Platelets > or equal to 100 x 109/Liii) Hemoglobin > or equal to 10 g/dLb) Hepatic functioni) Total bilirubin < or equal to 1 x Upper Normal Limitii) ASAT (SGOT) and ALAT (SGPT) < or equal to 1.5 x Upper Normal Limitiii) Alkaline phosphatase < or equal to 2.5 x Upper Normal Limitc) Renal function:i) Creatinine < or equal to 150 µmol/L (1.5 mg/dL); Complete staging work-up within 3 months prior to registration, including bilateral mammography, chest Xray (PA and lateral) and/or CT-scan, abdominal ultrasound and/or CT scan, bone scan. Patients must be accessible for treatment and follow-up. Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
Minimum age
18 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior systemic anticancer therapy for breast cancer (chemo-hormono-immuno-therapy). Prior radiation therapy for breast cancer. Pregnant, or lactating patients. Any locally advanced (clinical or pathological T4 and/or N2-known N3) or metastatic (M1) breast carcinoma. Patients with inoperable residual axillary nodal disease or with supraclavicular nodes.Pre-existing motor or sensory neurotoxicity of a severity > or equal to grade 2 by NCI criteria. Other serious illness or medical condition:o Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias.o History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.o Active uncontrolled infection.o Active peptic ulcer, unstable diabetes mellitus. Past or current history of other neoplasm except for:o Curatively treated basal cell skin cancer.o Adequately treated in situ carcinoma of the cervix. In regard to past or current history of other breast carcinoma, criteria of exclusion are:o Past history of ipsilateral or past/current history of contralateral invasive breast carcinoma.o Past or current history of contralateral ductal in situ breast carcinoma. A past or current history of ipsilateral ductal in situ or lobular in situ (ipsilateral or contralateral) breast carcinoma is not a criteria of exclusion. Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (< or equal to 20 mg methylprednisolone or equivalent). Concurrent treatment with hormonal replacement therapy: this treatment should be stopped before study entry. Definite contraindications for the use of corticosteroids. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry. Concurrent treatment with any other anti-cancer therapy.

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 telephone/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
1/06/1998
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
2730
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 21 0
Self funded/Unfunded
Name [1] 21 0
BIG (Breast International Group)
Country [1] 21 0
Australia
Funding source category [2] 22 0
Self funded/Unfunded
Name [2] 22 0
IBCSG (International Breast Cancer Study Group)
Country [2] 22 0
Australia
Funding source category [3] 23 0
Commercial sector/Industry
Name [3] 23 0
Sanofi-Aventis
Country [3] 23 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
sanofi-aventis
Talavera Corporate Centre
Building D
12-24 Talavera Road
Macquarie Park, NSW 2113
Address
to be confirmed
Country
France
Secondary sponsor category [1] 19 0
Other Collaborative groups
Name [1] 19 0
BIG (Breast International Group)
Address [1] 19 0
Breast International Group (BIG)-aisbl
Institut Jules Bordet
Blvd de Waterloo 121, 7th fl
B-1000 Brussels
Belgium
Country [1] 19 0
Australia
Secondary sponsor category [2] 20 0
Other Collaborative groups
Name [2] 20 0
IBCSG (International Breast Cancer Study Group)
Address [2] 20 0
International Breast Cancer Study Group IBCSG
Effingerstrasse 40
3008 Bern
Switzerland
Country [2] 20 0
Australia
Secondary sponsor category [3] 21 0
Other Collaborative groups
Name [3] 21 0
locked bag 7, HRMC, NSW 2310
Address [3] 21 0
trial now complete. No further information will be added due to time constraints.
Country [3] 21 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 214 0
Ashford Cancer Centre
Ethics committee address [1] 214 0
Ethics committee country [1] 214 0
Australia
Date submitted for ethics approval [1] 214 0
Approval date [1] 214 0
Ethics approval number [1] 214 0
Ethics committee name [2] 215 0
Auckland Hospital
Ethics committee address [2] 215 0
Ethics committee country [2] 215 0
New Zealand
Date submitted for ethics approval [2] 215 0
Approval date [2] 215 0
Ethics approval number [2] 215 0
Ethics committee name [3] 216 0
Austin & Repatriation Medical Centre
Ethics committee address [3] 216 0
Ethics committee country [3] 216 0
Australia
Date submitted for ethics approval [3] 216 0
Approval date [3] 216 0
Ethics approval number [3] 216 0
Ethics committee name [4] 217 0
Bendigo Hospital
Ethics committee address [4] 217 0
Ethics committee country [4] 217 0
Australia
Date submitted for ethics approval [4] 217 0
Approval date [4] 217 0
Ethics approval number [4] 217 0
Ethics committee name [5] 218 0
Border Medical Centre
Ethics committee address [5] 218 0
Ethics committee country [5] 218 0
Australia
Date submitted for ethics approval [5] 218 0
Approval date [5] 218 0
Ethics approval number [5] 218 0
Ethics committee name [6] 219 0
Box Hill Hospital
Ethics committee address [6] 219 0
Ethics committee country [6] 219 0
Australia
Date submitted for ethics approval [6] 219 0
Approval date [6] 219 0
Ethics approval number [6] 219 0
Ethics committee name [7] 220 0
Canberra Hospital
Ethics committee address [7] 220 0
Ethics committee country [7] 220 0
Australia
Date submitted for ethics approval [7] 220 0
Approval date [7] 220 0
Ethics approval number [7] 220 0
Ethics committee name [8] 221 0
Christchurch Hospital
Ethics committee address [8] 221 0
Ethics committee country [8] 221 0
New Zealand
Date submitted for ethics approval [8] 221 0
Approval date [8] 221 0
Ethics approval number [8] 221 0
Ethics committee name [9] 222 0
Concord Hospital
Ethics committee address [9] 222 0
Ethics committee country [9] 222 0
Australia
Date submitted for ethics approval [9] 222 0
Approval date [9] 222 0
Ethics approval number [9] 222 0
Ethics committee name [10] 223 0
Dunedin Hospital
Ethics committee address [10] 223 0
Ethics committee country [10] 223 0
New Zealand
Date submitted for ethics approval [10] 223 0
Approval date [10] 223 0
Ethics approval number [10] 223 0
Ethics committee name [11] 224 0
Flinders Medical Centre
Ethics committee address [11] 224 0
Ethics committee country [11] 224 0
Australia
Date submitted for ethics approval [11] 224 0
Approval date [11] 224 0
Ethics approval number [11] 224 0
Ethics committee name [12] 225 0
Frankston Hospital
Ethics committee address [12] 225 0
Ethics committee country [12] 225 0
Australia
Date submitted for ethics approval [12] 225 0
Approval date [12] 225 0
Ethics approval number [12] 225 0
Ethics committee name [13] 226 0
Geelong Hospital
Ethics committee address [13] 226 0
Ethics committee country [13] 226 0
Australia
Date submitted for ethics approval [13] 226 0
Approval date [13] 226 0
Ethics approval number [13] 226 0
Ethics committee name [14] 227 0
Lingard Hospital
Ethics committee address [14] 227 0
Ethics committee country [14] 227 0
Australia
Date submitted for ethics approval [14] 227 0
Approval date [14] 227 0
Ethics approval number [14] 227 0
Ethics committee name [15] 228 0
Liverpool Hospital
Ethics committee address [15] 228 0
Ethics committee country [15] 228 0
Australia
Date submitted for ethics approval [15] 228 0
Approval date [15] 228 0
Ethics approval number [15] 228 0
Ethics committee name [16] 229 0
Maroondah Hospital
Ethics committee address [16] 229 0
Ethics committee country [16] 229 0
Australia
Date submitted for ethics approval [16] 229 0
Approval date [16] 229 0
Ethics approval number [16] 229 0
Ethics committee name [17] 230 0
Monash Medical Centre
Ethics committee address [17] 230 0
Ethics committee country [17] 230 0
Australia
Date submitted for ethics approval [17] 230 0
Approval date [17] 230 0
Ethics approval number [17] 230 0
Ethics committee name [18] 231 0
Mount Hospital
Ethics committee address [18] 231 0
Ethics committee country [18] 231 0
Australia
Date submitted for ethics approval [18] 231 0
Approval date [18] 231 0
Ethics approval number [18] 231 0
Ethics committee name [19] 232 0
Newcastle Mater Hospital
Ethics committee address [19] 232 0
Ethics committee country [19] 232 0
Australia
Date submitted for ethics approval [19] 232 0
Approval date [19] 232 0
Ethics approval number [19] 232 0
Ethics committee name [20] 233 0
Palmerston North Hospital
Ethics committee address [20] 233 0
Ethics committee country [20] 233 0
New Zealand
Date submitted for ethics approval [20] 233 0
Approval date [20] 233 0
Ethics approval number [20] 233 0
Ethics committee name [21] 234 0
Peter MacCallum Cancer Institute
Ethics committee address [21] 234 0
Ethics committee country [21] 234 0
Australia
Date submitted for ethics approval [21] 234 0
Approval date [21] 234 0
Ethics approval number [21] 234 0
Ethics committee name [22] 235 0
Port Macquarie Hospital
Ethics committee address [22] 235 0
Ethics committee country [22] 235 0
Australia
Date submitted for ethics approval [22] 235 0
Approval date [22] 235 0
Ethics approval number [22] 235 0
Ethics committee name [23] 236 0
Prince of Wales Hospital
Ethics committee address [23] 236 0
Ethics committee country [23] 236 0
Australia
Date submitted for ethics approval [23] 236 0
Approval date [23] 236 0
Ethics approval number [23] 236 0
Ethics committee name [24] 237 0
Princess Alexandria Hospital
Ethics committee address [24] 237 0
Ethics committee country [24] 237 0
Australia
Date submitted for ethics approval [24] 237 0
Approval date [24] 237 0
Ethics approval number [24] 237 0
Ethics committee name [25] 238 0
Queen Elizabeth Hospital
Ethics committee address [25] 238 0
Ethics committee country [25] 238 0
Australia
Date submitted for ethics approval [25] 238 0
Approval date [25] 238 0
Ethics approval number [25] 238 0
Ethics committee name [26] 239 0
Royal Adelaide Hospital
Ethics committee address [26] 239 0
Ethics committee country [26] 239 0
Australia
Date submitted for ethics approval [26] 239 0
Approval date [26] 239 0
Ethics approval number [26] 239 0
Ethics committee name [27] 240 0
Royal Brisbane Hospital
Ethics committee address [27] 240 0
Ethics committee country [27] 240 0
Australia
Date submitted for ethics approval [27] 240 0
Approval date [27] 240 0
Ethics approval number [27] 240 0
Ethics committee name [28] 241 0
Royal Hobart Hospital
Ethics committee address [28] 241 0
Ethics committee country [28] 241 0
Australia
Date submitted for ethics approval [28] 241 0
Approval date [28] 241 0
Ethics approval number [28] 241 0
Ethics committee name [29] 242 0
Royal Melbourne Hospital
Ethics committee address [29] 242 0
Ethics committee country [29] 242 0
Australia
Date submitted for ethics approval [29] 242 0
Approval date [29] 242 0
Ethics approval number [29] 242 0
Ethics committee name [30] 243 0
Royal North Shore Hospital
Ethics committee address [30] 243 0
Ethics committee country [30] 243 0
Australia
Date submitted for ethics approval [30] 243 0
Approval date [30] 243 0
Ethics approval number [30] 243 0
Ethics committee name [31] 244 0
Royal Perth Hospital
Ethics committee address [31] 244 0
Ethics committee country [31] 244 0
Australia
Date submitted for ethics approval [31] 244 0
Approval date [31] 244 0
Ethics approval number [31] 244 0
Ethics committee name [32] 245 0
Royal Prince Alfred Hospital
Ethics committee address [32] 245 0
Ethics committee country [32] 245 0
Australia
Date submitted for ethics approval [32] 245 0
Approval date [32] 245 0
Ethics approval number [32] 245 0
Ethics committee name [33] 246 0
Sir Charles Gardiner Hospital
Ethics committee address [33] 246 0
Ethics committee country [33] 246 0
Australia
Date submitted for ethics approval [33] 246 0
Approval date [33] 246 0
Ethics approval number [33] 246 0
Ethics committee name [34] 247 0
St Andrew's Hospital
Ethics committee address [34] 247 0
Ethics committee country [34] 247 0
Australia
Date submitted for ethics approval [34] 247 0
Approval date [34] 247 0
Ethics approval number [34] 247 0
Ethics committee name [35] 248 0
St George Hospital
Ethics committee address [35] 248 0
Ethics committee country [35] 248 0
Australia
Date submitted for ethics approval [35] 248 0
Approval date [35] 248 0
Ethics approval number [35] 248 0
Ethics committee name [36] 249 0
St John of God Hospital (Subiaco)
Ethics committee address [36] 249 0
Ethics committee country [36] 249 0
Australia
Date submitted for ethics approval [36] 249 0
Approval date [36] 249 0
Ethics approval number [36] 249 0
Ethics committee name [37] 250 0
St Vincent's Hospital (Melbourne)
Ethics committee address [37] 250 0
Ethics committee country [37] 250 0
Australia
Date submitted for ethics approval [37] 250 0
Approval date [37] 250 0
Ethics approval number [37] 250 0
Ethics committee name [38] 251 0
The Alfred Hospital
Ethics committee address [38] 251 0
Ethics committee country [38] 251 0
Australia
Date submitted for ethics approval [38] 251 0
Approval date [38] 251 0
Ethics approval number [38] 251 0
Ethics committee name [39] 252 0
Western Hospital
Ethics committee address [39] 252 0
Ethics committee country [39] 252 0
Australia
Date submitted for ethics approval [39] 252 0
Approval date [39] 252 0
Ethics approval number [39] 252 0
Ethics committee name [40] 253 0
Westmead Hospital
Ethics committee address [40] 253 0
Ethics committee country [40] 253 0
Australia
Date submitted for ethics approval [40] 253 0
Approval date [40] 253 0
Ethics approval number [40] 253 0

Summary
Brief summary
This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+).

The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview conducted by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG). They have demonstrated the efficacy of adjuvant chemotherapy on reducing mortality and recurrence rates, but current regimens are far from optimal. Docetaxel (Taxotere), a new agent, has effectiveness and manageable side effects in the treatment of advanced breast cancer patients, and can plausibly improve outcomes for patients with early N+ breast cancer by optimal integration into current adjuvant chemotherapy regimens.

This clinical trial is designed to compare whether it is advantageous to use docetaxel and/or doxorubicin in combination or sequentially with other currently available chemotherapy drugs
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35831 0
Address 35831 0
Country 35831 0
Phone 35831 0
Fax 35831 0
Email 35831 0
Contact person for public queries
Name 10433 0
Administrative Officer, Data Management, Australia and New Zealand Breast Cancer Trial Group (ANZ BCTG) Operations Office
Address 10433 0
Australia and New Zealand Breast Cancer Trial Group (ANZ BCTG) Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Country 10433 0
Australia
Phone 10433 0
+61 2 4925 3068
Fax 10433 0
+61 2 49850141
Email 10433 0
[email protected]
Contact person for scientific queries
Name 1361 0
Professor John F Forbes
Address 1361 0
Australia and New Zealand Breast Cancer Trial Group (ANZ BCTG) Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Country 1361 0
Australia
Phone 1361 0
+61 2 49850113
Fax 1361 0
+61 2 49601539
Email 1361 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

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No documents have been uploaded by study researchers.

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