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Trial registered on ANZCTR


Registration number
ACTRN12609000500257
Ethics application status
Approved
Date submitted
12/12/2008
Date registered
23/06/2009
Date last updated
6/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase III trial to evaluate continuous versus intermittent combination chemotherapy in advanced breast cancer.
Scientific title
Phase III trial to evaluate continuous versus intermittent combination chemotherapy in advanced breast cancer. To determine whether any of the regimens is superior based on objective response rate, time to ultimate disease
progression, survival duration and quality of life.
Universal Trial Number (UTN)
Trial acronym
ANZ 8101
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 4127 0
Condition category
Condition code
Cancer 3515 3515 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients were randomised to receive continuous or intermittent therapy with Adriamycin intra venous (IV) 50 mg/m2 on day 1 plus Cyclophosphamide IV 750 mg/m2 on day 1 (AC) (21 day cycles), or Cyclophosphamide 100 mg/m2 orally day 1-14, Methotrexate 40 mg/m2 IV day 1 & 8, Fluorouracil 600 mg/m2 IV day 1 & 8, and Prednisone 40 mg/m2 orally day 1-14 (CMFP) (28 day cycles). For patients randomised to continuous AC therapy, cycles were repeated until disease progression, or until cumulative Adriamycin dosage of 450 mg/m2, after which the regimen changed to Vincristine 2 mg (total) IV day 1, Methotrexate 50 mg/m2 IV day 1 & 15, and Fluouracil 600 mg/m2 IV day 1 & 15 (VMF) (28 day cycles), given until disease progression or until 18 months after commencement of initial AC chemotherapy, whichever is earlier. Patients randomised to intermittent AC therapy received 3 cycles, those without progressive disease at that time will be observed without chemotherapy until disease progression. They will then receive AC for a maximum of 3 further cycles, if there is further disease progression after 2 cycles the patient will be off study treatment. Patients with complete response, partial response or stable disease after each 3 cycle block of AC will then be observed for a further period without therapy until disease progression, and at that time re-treated with 3 cycles of AC until a cumulative Adriamycin dose of 450 mg/m2 is reached, VMF will be substituted for AC in 3 cycle blocks until progressive disease. For patients randomised to continuous CMFP, cycles will be repeated until disease progression or for 18 months, whichever occurs sooner. Patients randomised to intermittent CMFP will receive 3 cycles, those without progressive disease at that time will be observed without chemotherapy until disease progression. They will then receive further CMFP for 3 cycles, if there is further disease progression after 2 cycles the patient will be off study treatment. Other patients will again be observed without treatment until disease progression and continue to receive blocks of 3 cycles of CMFP at each relapse until disease progression continues despite such therapy.
Intervention code [1] 3982 0
Treatment: Drugs
Comparator / control treatment
Continuous chemotherapy with either Adriamycin i.v. 50 mg/m2 on day 1 plus Cyclophosphamide i.v. 750 mg/m2 on day 1 (AC) (21 day cycles) or Cyclophosphamide 100 mg/m2 p.o. day 1-14, Methotrexate 40 mg/m2 i.v. day 1 & 8, Fluorouracil 600 mg/m2 i.v. day 1 & 8, and Prednisone 40 mg/m2 p.o. day 1-14 (CMFP) (28 day cycles). For patients randomised to continuous AC therpay cycles were repeated until disease progression, or cumulative Adriamycin dosage of 450 mg/m2, after which the regimen changed to Vincristine 2 mg (total) i.v. day 1, Methotrexate 50 mg/m2 i.v. day 1 & 15, and Fluouracil 600 mg/m2 i.v. day 1 & 15 (VMF) (28 day cycles), given until disease progression or until 18 months after commencement of initial AC chemotherapy, whichever is earlier. For patients randomised to continuous CMFP, cycles will be repeated until disease progression or for 18 months, whichever occurs sooner.
Control group
Active

Outcomes
Primary outcome [1] 4422 0
Objective response rate
Timepoint [1] 4422 0
Patient assessments as per investigations specified in the protocol, will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Primary outcome [2] 4423 0
Time to ultimate disease progression
Timepoint [2] 4423 0
Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments should continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Primary outcome [3] 4424 0
Quality of life
Timepoint [3] 4424 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments should continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [1] 7461 0
Assess the relationship of response rate, response duration and survival to prior adjuvant chemotherapy.
Timepoint [1] 7461 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [2] 7462 0
Assess the relationship of response rate, response duration and survival to prior hormonal therapy.
Timepoint [2] 7462 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [3] 7463 0
Assess the relationship of response rate, response duration and survival to performance status.
Timepoint [3] 7463 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [4] 7464 0
Assess the relationship of response rate, response duration and survival to toxicity.
Timepoint [4] 7464 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [5] 7465 0
Assess the relationship of response rate, response duration and survival to number of sites of metastatic involvement.
Timepoint [5] 7465 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.
Secondary outcome [6] 7466 0
Assess the relationship of response rate, response duration and survival to presence of visceral metastases.
Timepoint [6] 7466 0
Patient assessment will be made at completion of first 3 cycles of chemotherapy, and at 12 weekly intervals thereafter until disease progression. Patient assessment will be made on institution of relapse therapy, on suspicion of progressive disease and if progressive disease is confirmed subsequent assessments continue at 12 weekly intervals from day 1 of the new therapy, and if progressive disease is not confirmed assessment at 12 weekly intervals to continue. Patient assessment will be made on diagnosis of progressive disease at any time, and on patient withdrawal for any reason.

Eligibility
Key inclusion criteria
Histologically confirmed primary breast cancer with recurrent and/or metastatic disease. No previous cytotoxic chemotherapy for recurrent or metastatic breast cancer. Measurable or evaluable disease. Adequate marrow reserves. Performance status of 3 or better (0-3). Accessible for follow-up. Informed consent. Evidence of adequate renal and hepatic function, unless abnormality due to hepatic metastes.
Minimum age
N/A
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Past or current malignancies at other sites, except adequately treated squamous or basal cell carcinoma of the skin, or coned biopsied in situ carcinoma of the cervix. Radiotherapy in excess of regional therapy to primary disease, cranial therapy, or limited localised therapy. Past or present congestive cardiac failure, uncontrolled hypertension with left ventricular hypertrophy, left ventricular hypertrophy, or uncorrected left ventricular outflow obstruction. Patients whose only demonstratable malignancy is intracranial. Diabetes mellitus.

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/fax/computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated stratified blocks. Patients will be stratified according to performance status (0-2 or 3) and prior adjuvant chemotherapy.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/1982
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 949 0
2139
Recruitment postcode(s) [2] 950 0
3002
Recruitment postcode(s) [3] 951 0
2031
Recruitment postcode(s) [4] 952 0
5000
Recruitment postcode(s) [5] 953 0
7001
Recruitment postcode(s) [6] 954 0
2065
Recruitment postcode(s) [7] 955 0
6001
Recruitment postcode(s) [8] 956 0
2050
Recruitment postcode(s) [9] 957 0
3065
Recruitment postcode(s) [10] 958 0
2010
Recruitment postcode(s) [11] 964 0
6009
Recruitment outside Australia
Country [1] 1012 0
New Zealand
State/province [1] 1012 0
Auckland

Funding & Sponsors
Funding source category [1] 3555 0
Other Collaborative groups
Name [1] 3555 0
Ludwig Institute for Cancer Research
Country [1] 3555 0
Australia
Funding source category [2] 4288 0
Self funded/Unfunded
Name [2] 4288 0
Country [2] 4288 0
Primary sponsor type
Other Collaborative groups
Name
Ludwig Institute for Cancer Research
Address
Blackburn Building
University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 3203 0
None
Name [1] 3203 0
Address [1] 3203 0
Country [1] 3203 0

Ethics approval
Ethics application status
Approved

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

Contacts
Principal investigator
Name 28723 0
Address 28723 0
Country 28723 0
Phone 28723 0
Fax 28723 0
Email 28723 0
Contact person for public queries
Name 11880 0
Administrative Officer
Address 11880 0
Australian and New Zealand Breast Cancer Trial Group (ANZ BCTG) Operations Office
Calvary Mater Newcastle Hospital
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Country 11880 0
Australia
Phone 11880 0
+61 2 4925 3068
Fax 11880 0
+61 2 49850141
Email 11880 0
[email protected]
Contact person for scientific queries
Name 2808 0
Professor John F Forbes, Director of Research
Address 2808 0
Australian and New Zealand Breast Cancer Trial Group (ANZ BCTG) Operations Office
Calvary Mater Newcastle Hospital
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Country 2808 0
Australia
Phone 2808 0
+61 2 49850136
Fax 2808 0
+61 2 49601541
Email 2808 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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