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Trial registered on ANZCTR


Registration number
ACTRN12606000077561
Ethics application status
Approved
Date submitted
6/02/2006
Date registered
22/02/2006
Date last updated
30/04/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
IBCSG 32-05 / BIG 1-05 - Chemotherapy Adjuvant Study for women at advanced age
Scientific title
Phase III Trial Evaluating the Role of Adjuvant Pegylated Liposomal Doxorubicin (PLD, Caelyx®, Doxil®) for Women (age 66 years or older) with Endocrine Nonresponsive Breast Cancer Who Are NOT Suitable for Being Offered a "Standard Chemotherapy Regimen".
Secondary ID [1] 259625 0
Nil
Universal Trial Number (UTN)
Trial acronym
CASA - Chemotherapy Adjuvant Study for women at advanced Age
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 1041 0
Condition category
Condition code
Cancer 1118 1118 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IBCSG 32-05 / BIG 1-05 (CASA) is coordinated by the International Breast Cancer Study Group (IBCSG). The trial will be conducted in Australia and New Zealand by the ANZ Breast Cancer Trials Group.
The overall aim of the CASA study is to investigate the role of PLD as adjuvant chemotherapy for older postmenopausal women for whom chemotherapy is indicated, but standard regimens, derived from trials in younger women, are assumed to be too toxic or inconvenient. Some investigators are likely to choose no adjuvant cytotoxic therapy as a standard for frail patients at advanced age, while others will prefer to offer SOME treatment for all patients with endocrine nonresponsive disease. In order to take into consideration both attitudes towards the same problem, the IBCSG has designed two individual complementary randomized options in order to investigate the role of adjuvant cytotoxic chemotherapy for postmenopausal women at advanced age with endocrine nonresponsive early breast cancer.
Option 1 (designed for patients who, according to the treating physician and/or to the patient's preferences, are candidates to receive no adjuvant therapy):
a. PLD
b. No treatment
Option 2 (designed for patients who, according to the treating physician and/or to the patient's preferences, should receive some adjuvant treatment):
a. PLD
b. low dose metronomic cyclophosphamide and methotrexate (CM)
Note: Caelyx® (Doxil®), a PLD, is the experimental treatment.

PLD (Caelyx, Doxil) is administered intravenously at a dose of 20mg/m2 every 2 weeks for 16 weeks (total of 8 doses). Low-dose, metronomic cyclophosphamide and methotrexate (CM) is administered for 16 weeks. C = cyclophosphamide 50 mg/day orally continuously for 16 weeks; M = methotrexate 2.5 mg/twice a day orally days 1 and 4 of every week for 16 weeks.
Intervention code [1] 883 0
Treatment: Drugs
Comparator / control treatment
Pegylated Liposomal Doxorubicin (PLD) containing versus non-PLD containing regimens
Control group
Active

Outcomes
Primary outcome [1] 1495 0
Breast cancer free interval (BCFI) - BCFI is defined as the time from randomisation to local (including recurrence restricted to the breast after breast conserving treatment), regional, or distant relapse, or contralateral breast cancer. In calculating BCFI, second (non breast) malignancies are ignored and deaths without cancer event are censored at teh time of death. Appearance of ductal carcinoma in-situ (DCIS) or lobular carcinoma in-situ (LCIS) either in the ipsilateral or in the contralateral breast is not considered a BCFI event.
Timepoint [1] 1495 0
Three interim and one final analysis are planned with the timing of the interim efficacy analyses based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [1] 2683 0
Tolerability (percent of patients treated according to the protocol and completing the adjuvant program and percent protocol treatment received)
Timepoint [1] 2683 0
In order to evaluate short- and medium-term treatment effects, a longitudinal design is used including a baseline assessment (prior to randomisation), and assessments at 3, 6 and 12 months after randomisation. Tolerability will also be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [2] 2684 0
Adverse events
Timepoint [2] 2684 0
Adverse events will be assessed at follow-up visits occurring every 3 months for the first year, every 6 months for years 2-5 and yearly thereafter until death. Adverse events will also be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [3] 2685 0
Quality of life
Timepoint [3] 2685 0
In order to evaluate short- and medium-term treatment effects, a longitudinal design is used including a baseline assessment (prior to randomisation), and assessments at 3, 6 and 12 months after randomisation.
Secondary outcome [4] 2686 0
Disease-free survival (includes second malignancies and deaths)
Timepoint [4] 2686 0
Disease-free survival will be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [5] 2687 0
Sites of failure
Timepoint [5] 2687 0
Sites of failure will be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [6] 2688 0
Second (non-breast) malignancy
Timepoint [6] 2688 0
Second (non-breast) malignancy will be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [7] 2689 0
Overall survival
Timepoint [7] 2689 0
Overall survival will be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.
Secondary outcome [8] 2690 0
Competing causes of death.
Timepoint [8] 2690 0
Causes of death prior to breast cancer recurrence will be assessed during three interim and one final analysis. The timing of the interim efficacy analyses will be based upon both the number of breast cancer events and the median time that patients have been followed. The expected number of events for the overall pooled, final analysis is 258. The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The three other analyses will be performed approximately annually.

Eligibility
Key inclusion criteria
Histologically proven, hormone receptor negative, completely resected breast cancer confined to the breast and axillary nodes without detected metastases elsewhere; patients must not be candidates for endocrine therapy or standard chemotherapy regimen; margins must be negative for invasive breast cancer and DCIS; adequate bone marrow, renal, and hepatic function; adequate cardiovascular function and geographically accessible for follow-up.
Minimum age
66 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with locally advanced inoperable breast cancer; patients with a history of any prior ipsilateral or contralateral invasive breast cancer; patients with previous or concomitant malignancy diagnosed within the past five years; patients with other non-malignant uncontrolled systemic diseases; patients with myocardial infarction, pulmonary embolism or deep venous thrombosis within 6 months prior to randomisation; patients with significant malabsorption syndrome or disease affecting gastrointestinal tract function; prior neoadjuvant or adjuvant therapy for breast cancer; hormone replacement therapy (HRT); hormonal therapy, except steroids for adrenal failure, hormones for non-breast cancer related conditions; treatment with bisphosphonates, except for the treatment of osteoporosis.

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 a treatment code via a web-based randomisation system and treatment will be supplied in accordance with the randomisation allocation.
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
1/04/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1296
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,TAS

Funding & Sponsors
Funding source category [1] 1222 0
Self funded/Unfunded
Name [1] 1222 0
Australian New Zealand Breast Cancer Trials Group
Country [1] 1222 0
Australia
Funding source category [2] 1223 0
Other Collaborative groups
Name [2] 1223 0
International Breast Cancer Study Group
Country [2] 1223 0
Switzerland
Primary sponsor type
Other Collaborative groups
Name
Australian New Zealand Breast Cancer Trials Group
Address
Australian New Zealand Breast Cancer Trials Group
Department of Surgical Oncology
Calvary Mater Newcastle Hospital
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Australia
Country
Australia
Secondary sponsor category [1] 1080 0
Other Collaborative groups
Name [1] 1080 0
International Breast Cancer Study Group
Address [1] 1080 0
International Breast Cancer Study Group
Effingerstrasse 40
CH - 3008 BERN SWITZERLAND
Country [1] 1080 0
Switzerland

Ethics approval
Ethics application status
Approved

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

Contacts
Principal investigator
Name 35492 0
Address 35492 0
Country 35492 0
Phone 35492 0
Fax 35492 0
Email 35492 0
Contact person for public queries
Name 10072 0
Administrative Officer
Address 10072 0
Australian New Zealand Breast Cancer Trials Group
Department of Surgical Oncology
Calvary Mater Newcastle Hospital
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Australia
Country 10072 0
Australia
Phone 10072 0
+61 2 4925 3068
Fax 10072 0
+61 2 49850141
Email 10072 0
[email protected]
Contact person for scientific queries
Name 1000 0
Pofessor John Forbes, Director of Research, Australian New Zealand Breast Cancer Trials Group
Address 1000 0
Australian New Zealand Breast Cancer Trials Group
Department of Surgical Oncology
Calvary Mater Newcastle Hospital
Locked Bag 7
Hunter Region Mail Centre NSW 2310
Australia
Country 1000 0
Australia
Phone 1000 0
+61 2 4925 3068
Fax 1000 0
+61 2 49850141
Email 1000 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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