Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000191594
Ethics application status
Approved
Date submitted
11/04/2006
Date registered
24/05/2006
Date last updated
17/09/2023
Date data sharing statement initially provided
20/02/2023
Date results provided
20/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 0502 Neoadjuvant Gemcitabine
Scientific title
A phase II trial evaluating the efficacy and safety of epirubicin and cyclophosphamide (EC) followed by docetaxel and gemcitabine (DG) (+ trastuzumab if HER2 positive) as neoadjuvant chemotherapy for women with large operable or locally advanced breast carcinoma
Secondary ID [1] 285152 0
ANZ 0502
Universal Trial Number (UTN)
Trial acronym
ANZ 0502 NeoGem
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Large operable, or locally advanced breast carcinoma. 1166 0
Condition category
Condition code
Cancer 1251 1251 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive 4 cycles of epirubicin (90mg/m2, IV, Day 1) and cyclophosphamide (600mg/m2 IV, Day 1) followed by 4 cycles of Taxotere™ (docetaxel, 75mg/m2, IV, Day 1) and Gemzar® (gemcitabine, 1000mg/m2 IV, Days 1 & 8), with the addition of Herceptin® (trastuzumab) if the tumour is HER2 positive (trastuzumab: Cycle 1: 4mg/kg IV day 1, 2mg/kg IV day 8 & 15; Cycles 2-4, 2mg/kg IV day 1, 8 & 15; 6mg/kg IV day 22 of Cycle 4). Trastuzumab will be given for a total duration of one year (13 x 3 weekly cycles).

Larger operable and locally advanced tumours are associated with a poorer prognosis and a high risk of micrometastatic disease and require aggressive multimodality therapy. Anthracycline-based chemotherapy remains the core of most pre or postoperative chemotherapy regimens for early or locally advanced breast cancer unless contraindicated. Given promising data, including the established benefit of docetaxel in the adjuvant setting and the use of gemcitabine in metastatic breast cancer, suggesting non-cross resistance and synergy with the taxanes, a phase II study consisting of 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of docetaxel (day 1) and gemcitabine (day 1 & 8) each cycle delivered every three weeks is proposed. For patients with HER2 overexpressing breast cancer, the addition of trastuzumab to the docetaxel and gemcitabine treatment cycles aims to maximize synergy seen between all three agents and minimize cardiac toxicity. These regimens aim to maximize the pathologic complete response rate (pCR) rate which may translate into a survival benefit in the long term. Breast cancer tissue will also be obtained to correlate clinical and pathologic response with changes in molecular parameters.
Intervention code [1] 934 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 1688 0
To determine the pathologic complete response rate of the primary tumour in the breast (pCR) after epirubicin and cyclophosphamide (EC) followed by docetaxel and gemcitabine (DG) neoadjuvant chemotherapy in non-HER2 overexpressing breast cancer. Pathologic complete response is defined as no evidence of invasive tumour remaining in the breast at surgery following completion of chemotherapy.
Timepoint [1] 1688 0
Pathologic complete response will be measured after patients complete EC x 4 cycles, followed by DG/DGH x 4 cycles and at the completion of chemotherapy, following surgical resection.
Primary outcome [2] 1689 0
To determine the pathologic complete response rate of the primary tumour in the breast (pCR) after epirubicin and cyclophosphamide (EC) followed by docetaxel, gemcitabine and trastuzumab (DGH) neoadjuvant chemotherapy in HER2 overexpressing breast cancer (immunohistochemical staining 3+ or fluorescent in situ hybridization positive). Pathologic complete response is defined as no evidence of invasive tumour remaining in the breast at surgery following completion of chemotherapy.
Timepoint [2] 1689 0
Pathologic complete response will be measured after patients complete EC x 4 cycles, followed by DG/DGH x 4 cycles and at the completion of chemotherapy, following surgical resection.
Secondary outcome [1] 3028 0
To determine the clinical (assessed by palpation) and radiological (assessed by ultrasound) response rate, defined as disappearance of disease in the breast and axillary lymph nodes following 4 cycles of EC and 4 cycles of DG/DGH. To determine the safety profile of neoadjuvant EC followed by DG/DGH. To determine disease free and overall survival of patients during 24 months participation in the study. To document the sentinel node biopsy outcomes at the time of definitive surgery.
Timepoint [1] 3028 0
Clinical tumour assessments will be performed during each cycle of chemotherapy (three weekly). Radiological tumour assesments will be conducted before treatment, after participants have completed four cycles of chemotherapy (Epirubicin and Cyclophosphamide), and after completion of all chemothrapy treatment, prior to surgery. Sentinel node biopsy assessment will be conducted at the time of surgery, participants undergoing sentinel node biopsy will have an axillary disection as the same time to validate the sentinel node biopys outcomes. Disease free and overall survial assessments will be undertaken three monthly for a total of 18 months, following the completion of chemotherapy and surgery
Secondary outcome [2] 3029 0
All patients will be evaluable for toxicity from the time of their first treatment with chemotherapy. Expected toxicities and efficacy will be reviewed by the ANZ BCTG Independent Data Monitoring Committee (IDMC).
Timepoint [2] 3029 0
Treatment toxicity outcomes will be assessed during each chemotherapy cycle (three weekly).
Secondary outcome [3] 3030 0
Expected toxicities to be considered by the IDMC will be grade III/IV non haematological toxicity excluding alopecia, infection, nausea and vomiting, any grade. Grade II pneumonitis and grade III/IV cardiac events (congestive cardiac failure, cardiac death). The expected rates are 20% grade III/IV non haematological toxicities, 5% grade II pneumonitis and 4% grade III/IV cardiac events. If, after 20 patients have completed 8 cycles of treatment, one grade III cardiac event, two grade II incidences of pneumonitis and five grade III incidences of non-haematological toxicity occur this would trigger a review of the study by the IDMC.
Timepoint [3] 3030 0
Toxicity rates will be monitored after 20, 30 and 40 patients have completed at least 8 cycles of chemotherapy. The specific timing of these IDSMC reviews will be dependent on the time taken to recruit 20, 30 and 40 participants to the trial.

Eligibility
Key inclusion criteria
Female patients with a confirmed new diagnosis of unilateral, operable primary breast cancer, (clinically and/or on ultrasound), T2 (=3cm only), T3-4, N0-1, M0, diagnosed by core biopsy. The disease must be considered operable at first presentation. HER2 expression must be determined using either immunohistochemistry or FISH.• Patients with HER2 negative breast cancer must have a measured left ventricular ejection fraction of = 50% with MUGA or echocardiogram. Patients with HER2 positive breast cancer must have a measured left ventricular ejection fraction of = 55% with MUGA or echocardiogram.• No prior chemotherapy or hormonal therapy for breast cancer or other invasive cancer.• Adequate bone marrow, hepatic and renal function• ECOG performance status of 0, 1 or 2.• Women of child-bearing potential must have a negative pregnancy test and agree to use an accepted and effective method of non-hormonal contraception (barrier method of birth control; abstinence).• An ability to understand and the willingness to sign a written informed consent document.• Patients must be accessible for follow-up.• Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior chemotherapy or hormonal therapy for breast cancer or other invasive cancer.• Patients with inoperable, or inflammatory or metastatic breast cancer.• History of an active malignancy other than in situ carcinoma of the cervix, or non-melanomatous skin cancers in the last five years prior to registration to the study.• Patients may not be receiving any other investigational agents.• Congestive heart failure (New York Heart Association (NYHA) Class III-IV) or history of congestive failure, unstable angina pectoris, myocardial infarction in the last 6 months, poorly controlled hypertension (systolic >180 mmHg or diastolic > 100 mmHg), clinically significant valvular disease, or high risk uncontrolled arrhythmias. • History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.• Patients with dyspnoea at rest due to malignant or other disease or who require supportive oxygen therapy. • Patients who are pregnant or lactating at the time of registration to the trial. • Any active uncontrolled infection.• Any other medical condition which the investigator’s opinion makes the subject unsuitable for study participation.• Patients with a history of hypersensitivity reaction to products containing Polysorbate 80 (Tween).

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)
Patient eligibility will be determined by the investigator before registration to the study. The investigator or an authorized member of the trial team at the participating institution will contact the ANZBCTG Statistical Centre to register the patient and obtain the patient registration number. Patient registration numbers will be allocated sequentially as subjects enter the trial. Patients will be allocated to one of two treatment arms passed on HER2 status.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Safety concerns
Date of first participant enrolment
Anticipated
1/06/2006
Actual
30/08/2006
Date of last participant enrolment
Anticipated
1/06/2008
Actual
16/04/2009
Date of last data collection
Anticipated
Actual
15/02/2011
Sample size
Target
147
Accrual to date
Final
81
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD
Recruitment outside Australia
Country [1] 291 0
New Zealand
State/province [1] 291 0
Christchurch
Wellington

Funding & Sponsors
Funding source category [1] 1365 0
Self funded/Unfunded
Name [1] 1365 0
Australia and New Zealand Breast Cancer Trials Group
Country [1] 1365 0
Australia
Primary sponsor type
Other Collaborative groups
Name
ANZ Breast Cancer Trials Group Ltd.
Address
PO Box 155
HRMC NSW 2310
Country
Australia
Secondary sponsor category [1] 1205 0
None
Name [1] 1205 0
Nil
Address [1] 1205 0
Country [1] 1205 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6081 0
Royal Brisbane and Women's Hospital and Health Service District Office of the Human Research Ethics Committee
Ethics committee address [1] 6081 0
Ethics committee country [1] 6081 0
Australia
Date submitted for ethics approval [1] 6081 0
10/04/2006
Approval date [1] 6081 0
14/07/2006
Ethics approval number [1] 6081 0
2006/065

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

Contacts
Principal investigator
Name 36136 0
A/Prof Nicole McCarthy
Address 36136 0
Icon Cancer Care Wesley
Level 1, Wesley Medical Centre
40 Chasely Street
Auchenflower QLD 4066
Country 36136 0
Australia
Phone 36136 0
+61 (07) 3737 4636
Fax 36136 0
Email 36136 0
corinna.beckmore@bctrials.org.au
Contact person for public queries
Name 10123 0
John Forbes
Address 10123 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 10123 0
Australia
Phone 10123 0
+61 2 4925 3068
Fax 10123 0
+61 2 49850141
Email 10123 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 1051 0
John Forbes
Address 1051 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 1051 0
Australia
Phone 1051 0
+61 2 4925 3068
Fax 1051 0
+61 2 4985 0141
Email 1051 0
enquiries@anzbctg.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised Individual Patient Data (IPD) collected during the trial. The specific IPD to be shared (e.g. all data, published data, data of primary outcomes) will be as per the submitted research proposal and as assessed as appropriate by BCT.
When will data be available (start and end dates)?
Data will be made available for request after publication of the main/final study results; no end date.

Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines.
Available to whom?
Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Refer to the BCT Data Sharing Guidelines
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Subject to approval by Breast Cancer Trials concept@bctrials.org.au (refer to BCT Data Sharing Guidelines).


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Other https://researchdata.edu.au/a-phase-ii-0502-neogem/2538177  BCT Data Sharing Guidelines 1157-(Uploaded-18-08-2023-13-50-55)-Study-related document.pdf
Study protocol https://doi.org/10.58080/456k-n112 
Data dictionary https://doi.org/10.58080/456k-n112 


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes McCarthy N, Boyle F, Zdenkowski N, Bull J, Leong E... [More Details] 1157-(Uploaded-17-02-2023-10-16-45)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AINeoadjuvant chemotherapy with sequential anthracycline–docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)2014https://doi.org/10.1016/j.breast.2013.12.001
N.B. These documents automatically identified may not have been verified by the study sponsor.