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Trial registered on ANZCTR


Registration number
ACTRN12616000786493
Ethics application status
Approved
Date submitted
6/06/2016
Date registered
16/06/2016
Date last updated
16/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase II study of Paclitaxel and Epirubicin as Neoadjuvant Treatment for locally advanced Breast Cancer.
Scientific title
Phase II study of Paclitaxel and Epirubicin as Neoadjuvant Treatment for locally advanced Breast Cancer.
Secondary ID [1] 289361 0
TAX1471I-2-1
Universal Trial Number (UTN)
None
Trial acronym
NAB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 298994 0
Condition category
Condition code
Cancer 299058 299058 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Neoadjuvant therapy on day 1 of each cycle for 4 cycles (cycle duration is 3 weeks)
Epirubicin 90mg/m2 intravenously
Paclitaxel 175 mg/ m2 intravenously

Surgery
Surgical review 2-3 weeks after completion of neoadjuvant chemotherapy, if operable surgery planned for within the next week. Timing based on surgeon availability.
Surgery performed by specialist Breast Endocrine Surgical Unit. With larger tumours I.e. >5 cm original size, mastectomy recommended. Axillary dissection recommended for all patients. The duration of the surgical procedure is dependent on the tumour size, complexity of presentation and the procedure used.

Adjuvant chemotherapy will commence when patient is deemed by their treating Medical Oncologist to have fully recovered from surgery. Usual time frame anticipated to be 4-6 weeks post-operatively.
Adjuvant therapy (CMF) on days 1 and 8 of each cycle for 4 cycles (cycle duration is 4 weeks)
Cyclophosphamide 600 mg/m2 intravenously
Methotrexate 40 mg/ intravenously
Fluorouracil 600mg/m2 intravenously

Radiotherapy
Radiotherapy to chest wall/breast including supraclavicular node. Can begin any time after completion of the 1st cycle of CMF. Radiotherapy is planned for all patients and anticipated to commence no earlier than 2nd cycle of CMF chemotherapy, at the discretion of the treating Radiation Oncologist. Radiotherapy administered, including the dose, frequency and duration and any other relevant parameters at the discretion of the treating Radiation Oncologist.

Hormonal therapy
Tamoxifen 20mg orally per day administered to patients with ER +ve cancers to commence following the completion of all chemotherapy and radiotherapy. Planned duration of Tamoxifen therapy is 5 years. Patient compliance is monitored by patient self-report of dosing to treating Medical Oncologist.
Intervention code [1] 294948 0
Treatment: Drugs
Intervention code [2] 294949 0
Treatment: Surgery
Intervention code [3] 295021 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298542 0
Primary Outcome:
Clinical response rate of the combination of Paclitaxel and Epirubicin as neoadjuvant treatment with locally advanced carcinoma of the breast.

Outcome Measure: Clinical response assessed by physical examination of the breast by the Medical Oncologist.
Timepoint [1] 298542 0
Assessed at completion of neo-adjuvant chemotherapy with paclitaxel and epirubicin.
Primary outcome [2] 298637 0
Pathological response rate of the combination of Paclitaxel and Epirubicin as neoadjuvant treatment with locally advanced carcinoma of the breast.

Outcome Measure: Histopathological assessment of breast tissue biopsied during surgery.
Timepoint [2] 298637 0
At time of surgery
Secondary outcome [1] 324523 0
*Safety profile of the combination of Paclitaxel and Epirubicin in a neoadjuvant setting for locally advanced breast cancer.

Outcome Measure: All adverse events of any grade as defined by NCI CTCAE v 2.0. Adverse events may be self-reported or abnormal results of physical examinations, laboratory results or diagnostic imaging.
Timepoint [1] 324523 0
30 days post completion of Paclitaxel and Epirubicin
Secondary outcome [2] 324823 0
*Disease free survival

Outcome Measure:
CT scan of the chest, abdomen and pelvis, Mammogram and MRI as per usual clinical practice
Timepoint [2] 324823 0
At 10 years post completion of radiotherapy, with scans performed at the usual clinical practice frequency.
Secondary outcome [3] 324824 0
*Overall survival

Outcome Measure:
Patient survival status
Timepoint [3] 324824 0
At 10 years post completion of radiotherapy or until death.

Eligibility
Key inclusion criteria
1. Female aged 18 years or over with histological or cytologically confirmed locally advanced breast cancer. T3-4 Nx, Tx N2-3
2. No evidence of metastatic disease.
3. Normal cardiac function as determined by left ventricular injection fraction of greater that 50 % (gated heart pool scan or echocardiogram).
4. ECOG performance status of 0 or 1.
5. Must give written in form consent prior to commencement of any specific studies and any starting specific treatment.
6. Patients must be willing and able to comply with the protocol for the duration of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of metastatic disease.
2. Pregnant women or breast feeding mothers.
3. Women of child bearing potential who are unable or unwilling to use contraception.
4. Patients with a history of significant cardiac disease.
5. Patients with a history of significant neuropathy.
6. Patients with base line laboratory values with neutrophils less than 1.5 x 109/L, platelet count less than 100 x 109/L, serum creatinine greater than 1.5 x upper normal limit, serum bilirubin greater than 1.5 x upper normal limit, serum ALT or AST greater than 2.5 x upper normal limit, serum alkaline phosphatase greater than 2.5 x upper normal limit.
7. No patients with any prior malignancy other than completely excised basal cell carcinoma of the skin or completely resected cervical carcinoma in-situ.
8. Patients with any other uncontrolled medical condition or psychiatric condition deemed by the treating doctor to be unsuitable for treatment protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
SA
Recruitment hospital [1] 5914 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 5915 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 13361 0
5011 - Woodville South
Recruitment postcode(s) [2] 13362 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 293754 0
Commercial sector/Industry
Name [1] 293754 0
Bristol-Myers Squibb Pty Ltd
Address [1] 293754 0
556 Princes Highway
Noble Park
Victoria 3174
Country [1] 293754 0
Australia
Funding source category [2] 293755 0
Hospital
Name [2] 293755 0
The Queen Elizabeth Hospital
Address [2] 293755 0
28 Woodville Road
Woodville South
South Australia
5011
Country [2] 293755 0
Australia
Primary sponsor type
Hospital
Name
The Queen Elizabeth Hospital
Address
28 Woodville Road
Woodville South
South Australia
5011
Country
Australia
Secondary sponsor category [1] 292583 0
None
Name [1] 292583 0
Address [1] 292583 0
Country [1] 292583 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295192 0
North Western Adelaide Health Service Ethics of Human Research Committee
Ethics committee address [1] 295192 0
28 Woodville Road
Woodville South
South Australia
5011
Ethics committee country [1] 295192 0
Australia
Date submitted for ethics approval [1] 295192 0
05/05/2004
Approval date [1] 295192 0
26/05/2004
Ethics approval number [1] 295192 0
2004059

Summary
Brief summary
This phase II study will determine whether the combination of Paclitaxel and Epirubicin can be used safely in the neoadjuvant setting in women with locally advanced breast cancer. The study will determine whether, in a multi-centre setting, the activity of this combination is maintained with acceptable toxicity. The study will also determine the disease free survival and overall survival in patients with locally advanced breast cancer, treated with neoadjuvant Paclitaxel and Epirubicin followed by definitive local surgery and radiotherapy and adjuvant Cyclophosphamide Methotrexate Fluorouracil.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66406 0
A/Prof Ken Pittman
Address 66406 0
Level 8C, The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
South Australia
5011
Country 66406 0
Australia
Phone 66406 0
+61 8 82228474
Fax 66406 0
+61 8 82227486
Email 66406 0
ken.pittman@sa.gov.au
Contact person for public queries
Name 66407 0
Ms Sue Yeend
Address 66407 0
Level 8C, Clinical Trials, The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
South Australia
5011
Country 66407 0
Australia
Phone 66407 0
+61 8 82226148
Fax 66407 0
+61 8 82227486
Email 66407 0
sue.yeend@sa.gov.au
Contact person for scientific queries
Name 66408 0
A/Prof Ken Pittman
Address 66408 0
Level 8C, The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
South Australia
5011
Country 66408 0
Australia
Phone 66408 0
+61 8 82228474
Fax 66408 0
+61 8 82227486
Email 66408 0
ken.pittman@sa.gov.au

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