Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000095460
Ethics application status
Approved
Date submitted
25/10/1994
Date registered
25/10/1994
Date last updated
19/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
ANZ 8614: A phase III randomised trial of mitozantrone versus CMFP (cyclophosphamide, methotrexate, 5-flourouracil, prednisone) in advanced breast cancer – a quality of life study
Scientific title
ANZ 8614: A phase III randomised trial of mitozantrone versus CMFP in advanced breast cancer – a quality of life study
Secondary ID [1] 2 0
National Clinical Trials Registry: NCTR57
Universal Trial Number (UTN)
Trial acronym
ANZ 8614
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced breast cancer 2 0
Condition category
Condition code
Cancer 2 2 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ANZ 8614 is a phase III study evaluating mitozantrone versus CMFP in advanced breast cancer, with respect to patient quality of life.

Eligible patients shall be randomised to one of two treatment arms:
Arm A: mitozantrone initially, followed by second-line CMFP upon relapse (after previous response) or disease progression
Arm B: CMFP initially, followed by second-line mitozantrone upon relapse (after previous response) or disease progression

For both Arms (at the appropriate stage), mitozantrone is administered intravenously on day 1 of 21 day cycles at 14 mg per metre squared.

For both Arms (at the appropriate stage), CMF is administered in 28 day cycles as:
* cyclophosphamide, p.o. at 100 mg per square metre, on days 1-14 (inclusive);
* methotrexate, i.v. at 40 mg per square metre, on day 1 and day 8;
* 5-flourouracil, i.v. at 600 mg per square metre, on day 1 and day 8;
* prednisone, p.o. at 40 mg per square metre, on days 1-14 (inclusive);

All drug doses are based on the lesser of the patient’s ideal versus actual weight, and are subject to dose modifications (ie for toxicity) as specified in the protocol.

The same treatment duration criteria apply to both initial and second-line therapy, as follows:

* Mitozantrone treatment should continue until:
- disease progression, OR
- patient intolerance or unacceptable toxicity, OR
- cumulative dose of 140 mg per square metre is reached; (a greater cumulative dose is allowed at the discretion of the investigators, with cardiac monitoring).

* CMFP treatment should continue until:
- disease progression, OR
- patient intolerance or unacceptable toxicity, OR
- for at least 12 months duration; (a period of more than 12 months may be allowed in suitable patients, at the discretion of the investigator).
Intervention code [1] 1279 0
Treatment: Drugs
Comparator / control treatment
to be confirmed
Control group
Active

Outcomes
Primary outcome [1] 2 0
1. Time to disease progression
Timepoint [1] 2 0
Measured from the date of randomisation to the date of disease progression or death; assessed at 12 weekly intervals, at suspicion or diagnosis of progressive disease and/or at patient withdrawal (for any reason).
Primary outcome [2] 3 0
2. Overall survival
Timepoint [2] 3 0
Measured from the date of randomisation to the date of death.
Primary outcome [3] 4 0
3. Quality of life endpoints
Timepoint [3] 4 0
Measured using LASA (Linear Analogue Self Assessment) and QL-index (Quality of Life) instruments; assessed at baseline, prior to commencement of each treatment cycle (for the first 12 weeks of both first and second line therapy) and thereafter at 12 weekly assessments (including the “off treatment” follow up period).
Primary outcome [4] 5 0
4. Toxicity
Timepoint [4] 5 0
Recorded with each treatment cycle according to standard WHO (World Health Organisation) toxicity criteria (graded 1-4).
Primary outcome [5] 6 0
5. Objective response rate
Timepoint [5] 6 0
Taken from tumour measurements at 12 weekly intervals and at suspicion or diagnosis of progressive disease, or patient withdrawal.
Secondary outcome [1] 6 0
1. Activity of each treatment arm regimen on failure of initial therapy in a cross over design based on objective tumour response rates
Timepoint [1] 6 0
From tumour measurements at 12 weekly intervals from diagnosis of progressive disease until death or withdrawal.
Secondary outcome [2] 7 0
2. Assessment of new quality of life instruments for evaluating chemotherapy regimens in breast cancer.
Timepoint [2] 7 0
Assessed at baseline, prior to commencement of each treatment cycle (for the first 12 weeks of both first and second line therapy) and thereafter at 12 weekly assessments (including the “off treatment” follow up period) until withdrawal or death.

Eligibility
Key inclusion criteria
1. Histologically confirmed primary breast carcinoma with recurrent and/or metastatic disease 2. No previous cytotoxic chemotherapy for recurrent or metastatic breast cancer (see Special Considerations, point 2) 3. Measurable or evaluable disease (see Special Considerations, point 5) 4. Demonstrable adequate marrow reserves with WBC >/= 4.0 x 10^9/L and platelets >/= 100 x 10^9/L (unless depression is due to marrow metastases) 5. ECOG (Eastern Cooperative Oncology Group) performance status 0-3 (see Special Considerations, point 6) 6. Geographically accessible for follow-up 7. Informed consent in accordance with each institutions ethics review committee 8. Evidence of adequate renal function (creatinine < 0.15 S.I) and hepatic function (bilirubin < 20 S.I)
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Past or current malignancies at other sites, except adequately treated squamous or basal cell carcinoma of the skin or in-situ carcinoma of the cervix 2. Radiotherapy in excess of regional therapy to primary disease, cranial therapy, or limited localised therapy 3. Congestive cardiac failure or symptomatic coronary artery disease (see Special Considerations, point 4) 4. Patients whose only demonstrable malignancy is intracranial 5. Patients with known diabetes mellitus 6. Patients who are pregnant or breast feeding. Special Considerations:1. Patients are eligible for this study regardless of menopausal status or prior hormone therapy 2. Patients are eligible for inclusion following prior adjuvant cytotoxic chemotherapy, provided that a period not less than six (6) months elapsed between the cessation of adjuvant cytotoxic therapy and relapse 3. No upper age limit is specified; rather, entry will be at the discretion of the investigator 4. Patients with pre-existing cardiac disease without congestive cardiac failure may be entered at the investigator’s discretion providing cardiac monitoring is undertaken 5. Radiotherapy or surgery should not have been given or be planned to be given to the sole site(s) of measurable or evaluable disease6. Patients with liver metastases (bilirubin < 20 S.I.) or ECOG performance status 3 are eligible at

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
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation. Prior to randomisation, stratification will be performed according to performance status (0-1 versus 2-3), the presence of liver and/or brain metastases (versus neither) and institution.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Open (non-blinded study)
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/1988
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
450
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2 0
Self funded/Unfunded
Name [1] 2 0
Australian New Zealand Breast Cancer Trials Group (ANZ BCTG)
Country [1] 2 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian New Zealand Breast Cancer Trials Group (ANZ BCTG)
Address
to be confirmed
Country
Australia
Secondary sponsor category [1] 2 0
None
Name [1] 2 0
Nil
Address [1] 2 0
Country [1] 2 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 22 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 22 0
Ethics committee country [1] 22 0
Australia
Date submitted for ethics approval [1] 22 0
Approval date [1] 22 0
Ethics approval number [1] 22 0
Ethics committee name [2] 23 0
Auckland Hospital
Ethics committee address [2] 23 0
Ethics committee country [2] 23 0
New Zealand
Date submitted for ethics approval [2] 23 0
Approval date [2] 23 0
Ethics approval number [2] 23 0

Summary
Brief summary
In this protocol, mitozantrone as a single-agent will be compared with combination CMFP chemotherapy as initial chemotherapy in patients with advanced breast cancer. At the point of disease progression, patients will cross over to the other treatment arm. Comparison of treatment arms will be evaluated in terms of time to disease progression, overall survival, quality of life, toxicity and objective response rates. The design of this study allows the primary objective of determining optimal use of existing therapies with particular emphasis on improving quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35679 0
Address 35679 0
Country 35679 0
Phone 35679 0
Fax 35679 0
Email 35679 0
Contact person for public queries
Name 10468 0
Administrative Officer, Data Management Department
Address 10468 0
ANZ BCTG Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre
Newcastle NSW 2310
Country 10468 0
Australia
Phone 10468 0
+61 2 4925 3068
Fax 10468 0
+61 2 4985 0141
Email 10468 0
[email protected]
Contact person for scientific queries
Name 1396 0
Professor John F Forbes
Address 1396 0
ANZ BCTG Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre
Newcastle NSW 2310
Country 1396 0
Australia
Phone 1396 0
+61 2 4985 0113
Fax 1396 0
+61 2 4960 1539
Email 1396 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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