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Trial registered on ANZCTR


Registration number
ACTRN12605000355673
Ethics application status
Approved
Date submitted
9/09/2005
Date registered
9/09/2005
Date last updated
11/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
IBCSG 22-00 Maintenance Chemotherapy in Hormone Non-Responsive Breast Cancer
Scientific title
IBCSG 22-00 Maintenance Chemotherapy in Hormone Non-Responsive Breast Cancer withLow Dose Cytotoxics as Anti-angiogenesis treatment Following Adjuvant Induction Chemotherapy for patients with ER-negative and PgR-negative Breast Cancer
Secondary ID [1] 148 0
National Clinical Trials Registry: NCTR403
Universal Trial Number (UTN)
Trial acronym
IBCSG 22-00
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adjuvant Breast Cancer 449 0
Condition category
Condition code
Cancer 526 526 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IBCSG 22-00 is co-ordinated internationally by the International Breast Cancer Study Group (IBCSG). The trial is conducted in Australia and New Zealand by the Australian New Zealand Breast Cancer Trials Group.
This protocol is designed to determine if maintenance chemotherapy with low dose cyclophosphamide and methotrexate given for 12 months following 3 to 6 months of induction cytotoxic chemotherapy improves outcome compared with induction chemotherapy alone. The maintenance chemotherapy (CM) regimen has demonstrated activity in metastatic breast cancer and an interference with angiogenic serum factors. It is hypothesized that this regimen will delay tumor recurrence.

IBCSG 22-00 is an international, multicentre, clinical trial of 900 patients who have had histologically or cytologically confirmed, receptor-negative primary breast cancer.

Women will be randomised in a 2-arm design to receive one of the following:

a. Induction Chemotherapy
b. Induction Chemotherapy followed by 12 months maintenance chemotherapy

Patients randomised to the chemotherapy maintenance arm will receive oral low dose chemotherapy consisting of 50mg cyclophosphamide daily for one year and 2.5mg methotrexate twice a day, days 1 and 2 every week for one year.
Intervention code [1] 425 0
Treatment: Drugs
Comparator / control treatment
Induction Chemotherapy. Induction Chemotherapy regimens approved by the IBCSG, will be administered at the physicians discretion.
Control group
Historical

Outcomes
Primary outcome [1] 604 0
To evaluate the efficacy of a low-dose chemotherapy regimen, hypothesized to have anti-angiogenic activity, administered following a standard chemotherapy program in patients whose tumors are not endocrine therapy-responsive. Two interim and one final analysis are planned, with an accrual rate of 180 evaluable patients per year, 3.5 years of accrual and 5 years of additional follow-up is considered sufficient.
Timepoint [1] 604 0
Two interim and one final analyses will be performed during the conduct of the study. A total of 256 events is required to detect an improvement in five year disease-free survival so interim analyses will be planned after 102 and 179 events have been observed.
Primary outcome [2] 5396 0
Overall survival - defined as the time from randomisation to death from any cause
Timepoint [2] 5396 0
Two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Primary outcome [3] 5397 0
Systemic disease-free survival - defined as the time from randomisation to systemic relapse, appearance of second (non-breast) primary tumour, or death, whichever occurs first.
Timepoint [3] 5397 0
Two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Primary outcome [4] 5398 0
Toxicity - will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC).
Timepoint [4] 5398 0
Two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Primary outcome [5] 5399 0
Quality of Life (QoL) will be assessed using a questionnaire completed by the patient at each scheduled QoL follow-up.
Timepoint [5] 5399 0
Quality of Life (QoL) will be assessed at months 9, 12, 18 and 24 using the date induction chemotherapy began as day 0; thereafter, QoL will be followed at months 36, 48, 60 and 72
Secondary outcome [1] 1267 0
Systemic relapse - defined as any recurrent or metastatic disease in sites other than the local mastectomy scar/chest wall/skin, the ipsilateral breast in case of breast conservation, or the contralateral breast.
Timepoint [1] 1267 0
Patients are followed every 6 months for 5 years and then annually thereafter and two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Secondary outcome [2] 9070 0
Sites of first recurrence - including local, regional, contralateral breast and distant.
Timepoint [2] 9070 0
Patients are followed every 6 months for 5 years and then annually thereafter and two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Secondary outcome [3] 9071 0
Incidence of second (non-breast) malignancies - determined as the time of first appearance of a suspicious lesion, later proven to be a definitive recurrence or metastasis.
Timepoint [3] 9071 0
Patients are followed every 6 months for 5 years and then annually thereafter and two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.
Secondary outcome [4] 9072 0
Causes of death without relapse of breast cancer - determined as any death related to causes other than breast cancer.
Timepoint [4] 9072 0
Patients are followed every 6 months for 5 years and then annually thereafter and two interim analyses are planned prior to reaching five years of median follow-up. the target number of events for the study is 256, so interim analyses will be planned after 102 and 179 events have been observed.

Eligibility
Key inclusion criteria
Premenopausal or postmenopausal patients with histologically proven, receptor-negative primary breast cancer who are in adequate health to begin or continue with induction chemotherapy, have completed baseline Quality of Life forms, are geographically accessible for follow-up and have signed written informed consent.
Minimum age
Not stated
Maximum age
Not stated
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with bilateral disease, positive margins in the resected tumour specimen, previous or concomitant malignancy, patients who have received prior therapy for breast cancer, or who have non-malignant systemic diseases that would prevent them from undergoing any trial treatment options, or who are pregnant or lactating within 6 months of diagnosis.

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)
The ANZ BCTG Statistical Centre at the NHMRC Clinical Trials Centre, University of Sydney will provide a central randomisation service by fax for all Australian and New Zealand institutions. At the time of study entry all participants will be allocated to either commence or complete planned induction chemotherapy alone, or to receive 12 months of chemotherapy maintenance therapy following planned induction chemotherapy.
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
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,VIC,QLD,SA

Funding & Sponsors
Funding source category [1] 585 0
Self funded/Unfunded
Name [1] 585 0
Australia and New Zealand Breast Cancer Trials Group
Address [1] 585 0
ANZBCTG
PO Box 155
HRMC NSW 2310
Country [1] 585 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Breast Cancer Trials Group
Address
PO Box 155
Hunter Region Mail Centre NSW 2310
Country
Australia
Secondary sponsor category [1] 474 0
Other Collaborative groups
Name [1] 474 0
International Breast Cancer Study Group
Address [1] 474 0
IBCSG Coordinating Center
Effingerstrasse 40
3008 Bern
SWITZERLAND
Country [1] 474 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1604 0
Tweed Hospital
Ethics committee address [1] 1604 0
Ethics committee country [1] 1604 0
Australia
Date submitted for ethics approval [1] 1604 0
Approval date [1] 1604 0
23/11/2004
Ethics approval number [1] 1604 0
Ethics committee name [2] 1605 0
Border Medical Oncology
Ethics committee address [2] 1605 0
Ethics committee country [2] 1605 0
Australia
Date submitted for ethics approval [2] 1605 0
Approval date [2] 1605 0
20/03/2002
Ethics approval number [2] 1605 0
Ethics committee name [3] 1606 0
Box Hill Hospital
Ethics committee address [3] 1606 0
Ethics committee country [3] 1606 0
Australia
Date submitted for ethics approval [3] 1606 0
Approval date [3] 1606 0
07/04/2005
Ethics approval number [3] 1606 0
Ethics committee name [4] 1607 0
Maroondah Hospital
Ethics committee address [4] 1607 0
Ethics committee country [4] 1607 0
Australia
Date submitted for ethics approval [4] 1607 0
Approval date [4] 1607 0
07/04/2005
Ethics approval number [4] 1607 0
Ethics committee name [5] 1608 0
Toowoomba Hospital
Ethics committee address [5] 1608 0
Ethics committee country [5] 1608 0
Australia
Date submitted for ethics approval [5] 1608 0
Approval date [5] 1608 0
17/10/2002
Ethics approval number [5] 1608 0
Ethics committee name [6] 1609 0
The Queen Elizabeth Hospital
Ethics committee address [6] 1609 0
Ethics committee country [6] 1609 0
Australia
Date submitted for ethics approval [6] 1609 0
Approval date [6] 1609 0
Ethics approval number [6] 1609 0
Ethics committee name [7] 1610 0
Christchurch Hospital
Ethics committee address [7] 1610 0
Ethics committee country [7] 1610 0
New Zealand
Date submitted for ethics approval [7] 1610 0
Approval date [7] 1610 0
18/11/2002
Ethics approval number [7] 1610 0

Summary
Brief summary
This study aims to evaluate the efficacy of maintenance chemotherapy in women with hormone non-responsive breast cancer.

Who is it for?
You may be eligible join this study if you are a woman with receptor-negative primary breast cancer and are in adequate health to begin or continue with induction chemotherapy.

Trial details
Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will undergo induction chemotherapy followed by maintenance chemotherapy. Maintenance chemotherapy involves taking one 50mg cyclophosphamide tablet daily for one year and two 2.5mg methotrexate tablets twice a day on days 1 and 2 of every week for one year. Participants in the other group will undergo induction chemotherapy only. This will be administered at the doctor's discretion.

Participants will be regularly assessed over the duration of the trial to determine whether maintenance chemotherapy delays tumor recurrence and prolongs survival.
Trial website
Trial related presentations / publications
Public notes
Please note that date of first participant entry into the trial reflects International recruitment, which began before the trial opened in Australia.

Contacts
Principal investigator
Name 36343 0
Prof John F. Forbes
Address 36343 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 36343 0
Australia
Phone 36343 0
+61 2 4925 3068
Fax 36343 0
+61 2 4985 0141
Email 36343 0
enquiries@anzbctg.org
Contact person for public queries
Name 9614 0
Prof John F. Forbes
Address 9614 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 9614 0
Australia
Phone 9614 0
+61 2 4925 3068
Fax 9614 0
+61 2 49850141
Email 9614 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 542 0
Prof John F. Forbes, Director of Research
Address 542 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 542 0
Australia
Phone 542 0
+61 2 4925 3068
Fax 542 0
+61 2 49850141
Email 542 0
enquiries@anzbctg.org

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary