Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000119796
Ethics application status
Approved
Date submitted
16/01/2013
Date registered
31/01/2013
Date last updated
14/01/2021
Date data sharing statement initially provided
17/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Neoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancer
Scientific title
Phase III, open-label, randomised trial of nab-paclitaxel versus paclitaxel in patients with HER2-negative, not metastatic unilateral breast cancer who are at risk of disease recurrence to assess treatment response
Secondary ID [1] 281752 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
ETNA (Evaluating Treatment with Neoadjuvant Abraxane)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 288062 0
Condition category
Condition code
Cancer 288434 288434 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive 4 cycles of Abraxane (Investigational Product) (125mg/m2) intravenously over 30 min given week 1, 2 and 3 followed by 1 week rest or the comparator. This will be followed by 4 cycles of anthracycline-containing chemotherapy (AC/EC or FEC - based on clinician decision). AC Doxorubicin 60mg/m2, Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks; EC Epirubicin 90mg/m2, Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks; FEC Fluorouracil 600mg/m2 Epirubicin 90mg/m2 Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks
Intervention code [1] 286298 0
Treatment: Drugs
Comparator / control treatment
Subjects will receive 4 cycles of paclitaxel (90mg/m2 diluted in 250mL of WFI) intravenously over 1 hour given week 1, 2 and 3 followed by 1 week rest.
This will be followed by 4 cycles of anthracycline-containing chemotherapy (AC/EC or FEC- based on clinician decision). AC Doxorubicin 60mg/m2, Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks; EC Epirubicin 90mg/m2, Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks; FEC Fluorouracil 600mg/m2 Epirubicin 90mg/m2 Cyclophosphamide 600mg/m2 intravenously over 30 min given once every 3 weeks
Control group
Active

Outcomes
Primary outcome [1] 288609 0
The primary endpoint is to compare the rate of pathological Complete response (pCR) at surgery between abraxane and paclitaxel containing regimens.
Timepoint [1] 288609 0
At the time of surgery the absence of invasive disease in breast and nodes will be measured by histopathological examination. Surgery will occur between 3 to 5 weeks following last cycle of chemotherapy.
Secondary outcome [1] 300587 0
clinical Overall Response (cOR) after the first 4 cycles of abraxane vs paclitaxel, and after the entire pre-operative chemotherapy (before surgery) in the study arms of abraxane vs paclitaxel
Timepoint [1] 300587 0
after 4 cycles and before surgery by palpation of the breast and axilla.
Secondary outcome [2] 300588 0
to compare Event Free Survival (Distant, Local, Regional) in the study arms of abraxane vs paclitaxel
Timepoint [2] 300588 0
diagnosis of breast cancer progression during treatment or recurrence after surgery will be assessed by the investigator and confirmed by clinical, laboratory, radiological and/or histological findings. The protocol defines what is considered acceptable to confirm the event free survivals listed above. After surgery patients will be follwed up for 10 years after surgery.
Secondary outcome [3] 300589 0
Overall Survival in the study arms of abraxane vs paclitaxel
Timepoint [3] 300589 0
Overall Survival is defined as the time from randomisation to the date of death. Patients alive at the end of the study (10 years) will be considered at their last contact.
Secondary outcome [4] 300590 0
Evaluation of the tolerability of the treatment regimens in the different study arms will be measured by using the Common Terminology Criteria for Adverse Events (CTCAE) verison 4.0
Timepoint [4] 300590 0
Duration of study up to 28 days after treatment (if surgery not performed) or surgery
Secondary outcome [5] 300591 0
to conduct molecular and clinical analyses to assess the presence of predictive markers of benefit
Timepoint [5] 300591 0
Tumour tissue blocks at diagnosis and at surgery are mandatory. bloods/serum and plasma at baseline and after the chemotherapy treatment is optional. Further tissue samples at other time points are optional and defined in the protocol

Eligibility
Key inclusion criteria
Patients with HER-2 negative, invasive unilateral breast cancer with known hormone receptor status and tumour grade. ECOG status 0 or 1.
Clinical stage should be either
- T2, T3, T4 disease, triple negative
- T2, T3, T4 disease, ER or PgR positive and moderately differentiated or poorly differentiated tumour grade (G II-III).
Paraffin-embedded tumour block should be available for central confirmation of eligiblity criteria.
Written consent
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- contralateral breast cancer or presence of metastatic disease (exception: contralateral in situ ductal cancer)
- surgical axillary staging prior to study entry (exception: FNA of 1 axillary node is permitted, and, but not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes)
- pregnant and lactating women.
- women with childbearing potential unless appropriate contraception as described in protocol
- treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for current diagnosed breast cancer.
- previous investigational product within 4 weeks of randomisation
- patients on therapy with a strong CYP3A4 ihibitor, and on therapy with warferin
- previous or concomitant malignancy of other type that could affect compliance.
- pre-existing motor or sensory neuropathy of Grade >1 for any reason
- patients with hypersensitivity due to drugs containing polyoxyethylene castor oil, or hardened castor oil.
- other serious illness or medical condition (examples included in the protocol)
- patients with a history of uncontrolled seizures, contral nervous system disorders or psychaitric disability judged to be clinically significant
- serious uncontrolled infections or poorly controlled diabetes mellitus
- Abonrmal laboratory values at baseline: ANC <1.5 x 109/L; platelet count < 100 x 109/L; Hb < 10g/dL; serum total bilirubin > 1.5xULN (except documented Gilbert's syndrome); ALT > 1.25 x ULN; serum creatinine > 1.5x ULN
- Baseline LVEF < 50% by echocardiography or MUGA scan


-

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)
Subject to meeting all eligibility criteria, the Sponsor will confirm eligibility and via the Electronic Data CApture system the patient will be automatically randomised according to the stratification variables being:
a) cooperative research group
b) disease stage (operable and locally advanced)
c) tumour subtype (triple negative vs luminal B high and luminal B intermediate)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised to one of the 2 possible treatments arms in a 1:1 ratio (abraxane vs paclitaxel) using Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Patients will be stratified by Cooperative Research Group, Operable (T2N0-1; T3N0) versus locally advanced (T3N1, T4, anyN2N3); and tumour sub-type (Luminal B intermediate Her2 negative, ER/PR positive Ki67 14-20% vs Luminal B high Her2 negative, ER/PR positive Ki67>20% vs Triple negative Her2 negative, ER and PR negative)
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
Active, not recruiting
Date of first participant enrolment
Anticipated
17/04/2013
Actual
1/08/2013
Date of last participant enrolment
Anticipated
Actual
10/02/2015
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
632
Accrual to date
Final
695
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA,VIC
Recruitment hospital [1] 1229 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 1577 0
Maroondah Hospital - Ringwood East
Recruitment hospital [3] 1578 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 4388 0
Breast Cancer Research Centre - Western Australia - Perth
Recruitment outside Australia
Country [1] 4792 0
Italy
State/province [1] 4792 0
Country [2] 4793 0
Poland
State/province [2] 4793 0
Country [3] 4794 0
Germany
State/province [3] 4794 0
Country [4] 4795 0
Russian Federation
State/province [4] 4795 0
Country [5] 4796 0
Austria
State/province [5] 4796 0
Country [6] 4797 0
Singapore
State/province [6] 4797 0

Funding & Sponsors
Funding source category [1] 286565 0
Commercial sector/Industry
Name [1] 286565 0
Investigator Initiated Research Grant from Celgene
Country [1] 286565 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
Fondazione Michelangelo
Address
Michelangelo Operations Office
c/o Fondazione IRCCS Istituto Nazionale dei Tumori
Via G. Venezian, 1
20133 Milano
Country
Italy
Secondary sponsor category [1] 285350 0
Other
Name [1] 285350 0
Breast Cancer Research Centre of Western Australia (BCRC-WA)
Address [1] 285350 0
Hollywood Private Hospital
Entrance 3, Lower Ground Floor
101 Monash Avenue
Nedlands WA 6009
Country [1] 285350 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288632 0
Mount Ethics Committee
Ethics committee address [1] 288632 0
Ethics committee country [1] 288632 0
Australia
Date submitted for ethics approval [1] 288632 0
26/02/2013
Approval date [1] 288632 0
16/04/2013
Ethics approval number [1] 288632 0
EC74.2
Ethics committee name [2] 295041 0
Hollywood Private Hospital Research Ethics Commitee
Ethics committee address [2] 295041 0
Ethics committee country [2] 295041 0
Australia
Date submitted for ethics approval [2] 295041 0
18/01/2016
Approval date [2] 295041 0
25/02/2016
Ethics approval number [2] 295041 0

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

Contacts
Principal investigator
Name 36938 0
Prof Arlene Chan
Address 36938 0
Breast Cancer Research Centre,-WA, Suite 407, Hollywood Consulting Centre, 91 Monash Avenue, Nedlands, 6009 WA
Country 36938 0
Australia
Phone 36938 0
+61 8 9481 4522
Fax 36938 0
Email 36938 0
[email protected]
Contact person for public queries
Name 36939 0
Arlene Chan
Address 36939 0
Breast Cancer Research Centre,-WA, Suite 407, Hollywood Consulting Centre, 91 Monash Avenue, Nedlands, 6009 WA
Country 36939 0
Australia
Phone 36939 0
+61 8 9481 4522
Fax 36939 0
Email 36939 0
[email protected]
Contact person for scientific queries
Name 36940 0
Arlene Chan
Address 36940 0
Breast Cancer Research Centre,-WA, Suite 407, Hollywood Consulting Centre, 91 Monash Avenue, Nedlands, 6009 WA
Country 36940 0
Australia
Phone 36940 0
+61 8 9481 4522
Fax 36940 0
Email 36940 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.