Plain English Summary
Background and study aims
Breast cancer is the most common type of cancer in the UK. Chemotherapy treatment involves using drugs to kill the cancer cells. Chemotherapy can be used before surgery to shrink large tumours or tumours that have spread within the breast region (locally advanced), in order to make the surgery possible or less disfiguring. This is called neo-adjuvant chemotherapy. The aim of this study is to find out whether adding capecitabine to the standard treatment of adriamycin, cyclophosphamide and docetaxel increases the anti-cancer response.
Who can participate?
Women between 18 and 75 years of age with large or locally advanced breast cancer
What does the study involve?
All patients receive adriamycin and cyclophosphamide. Patients who respond well receive further courses and are randomly allocated to receive either docetaxel or a combination of docetaxel with capecitabine. Patients who do not respond well to adriamycin and cyclophosphamide are randomly allocated to receive either docetaxel or a combination of docetaxel with capecitabine. Patients are treated with lenograstim on days 2-6 of each cycle of chemotherapy.
What are the possible benefits and risks of participating?
Possible benefits of the treatment include enhanced anti-cancer response and reduced toxicity (side effects). All patients receiving chemotherapy are at risk of side effects from the drugs used.
When is the study starting and how long is it expected to run for?
November 2008 to December 2011
Who is funding the study?
Roche, Sanofi Aventis and Chugai Pharma (UK)
Who is the main contact?
Prof. Oleg Eremin
oleg.eremin@ulh.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Oleg Eremin
ORCID ID
Contact details
Lincoln County Hospital
Greetwell Road
Lincoln
LN2 2QY
United Kingdom
+44 (0)1522 573 872
oleg.eremin@ulh.nhs.uk
Additional identifiers
EudraCT number
2007-003221-25
ClinicalTrials.gov number
Protocol/serial number
07H0406260
Study information
Scientific title
A phase II, single-centre, randomised study of the effectiveness of the addition of Capecitabine to a standard regimen containing Adriamycin®, Cyclophosphamide and Docetaxel as neoadjuvant treatment in large or locally advanced breast cancers
Acronym
XINACT
Study hypothesis
The addition of capecitabine to Adriamycin®, cyclophosphamide and docetaxel in the neoadjuvant setting improves the pathological response rate in patients with large or locally advanced breast cancer
Ethics approval
Leicestershire, Northamptonshire & Rutland Ethics Committee, 06/06/2008, ref: NAC071
Study design
Single-centre randomised study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the conatct details below to request a patient information sheet
Condition
Large or locally advanced breast cancer
Intervention
1. All patients will receive adriamycin (A, 60 mg/m2, iv three weekly) and cyclophosphamide (C, 600 mg/m2, iv three weekly)
2. Patients who respond to two courses of AC will be randomised to continue to receive two further courses of AC followed by either four courses of docetaxel (100 mg/m2, iv three weekly) [Group A] or will receive a combination of docetaxel (75 mg/m2, iv three weekly) with capecitabine (2,000 mg/m2, orally in two divided doses for two out of three weeks) [Group B]
3. Nonresponders will be randomised to receive either docetaxel (100 mg/m2, iv three weekly) for up to six courses [Group C] or a combination of docetaxel (75 mg/m2, iv three weekly) with capecitabine (2,000 mg/m2, orally in two divided doses for two out of three weeks) [Group D]
4. Lenograstim will be given at 263 µg daily by sc injection on days 2-6 of each cycle of chemotherapy after stratification
Intervention type
Drug
Phase
Phase II
Drug names
Adriamycin®, Cyclophosphamide, Docetaxel, Lenograstim
Primary outcome measures
Pathological response in the breast and axilla, as assessed by the pathologist, following completion of chemotherapy and surgery, using established criteria. The chemotherapy is given over 24 weeks, the surgery is carried out 4 weeks later, and the pathology is available 2 weeks after surgery
Secondary outcome measures
1. Firstly, to document the QoL and related morbidity with these novel drug combinations, including the use of granulocyte colonomy stimulating factor (G-CSF) in a primary prophylactic setting
2. The quality of life assessment is carried out during the study, the last questionnaire is filled after the last cycle of chemotherapy
3. The questionnaires data is entered into an SPSS database and will be evaluated at the end of the trial
4. To define, accurately and reliably, the predictive value of response to chemotherapy of specific proteins/genes, previously identified and characterised in an in vitro study
5. To evaluate the host defences in the contribution of these defences to the beneficial effects documented, women with breast cancer undergoing chemotherapy
6. To assess the effectiveness of MRM as a predictor of early clinical response to neoadjuvant chemotherapy (NAC). The magnetic resonance mammography findings are entered into an SPSS database and will be evaluated at the end of the trial
7. The genomic/proteomic and immune parameters are ongoing studies which will continue for an unspecified period after completion of the clinical part of the study
Overall trial start date
01/11/2008
Overall trial end date
30/12/2011
Reason abandoned
Eligibility
Participant inclusion criteria
1. Women with histologically confirmed carcinoma of the breast, with measurable or evaluable large (greater than or equal to 3 cm) or locally advanced (T3, T4, TxN2) disease
2. Women who are over 18 and under 75 years and able to sign the informed consent
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
130
Participant exclusion criteria
1. World Health Organisation (WHO) performance status 2, 3 and 4
2. Prior chemotherapy or radiotherapy unless for basal cell carcinoma
3. Unstable angina and/or evidence of significant cardiac dysfunction
4. Patients who have diabetes requiring insulin
5. Pregnancy or lactation
6. Inadequate organ function, as evidenced by any of the following laboratory values:
6.1. Absolute neutrophil count < 1500/uL
6.2. Platelet count < 100,000/uL
6.3. Total bilirubin > 1.5 mg/dL
6.4. Alkaline phosphatase, AST, and/or ALT > 2x upper limit of normal
6.5. Serum creatinine > 2.0 mg/dL
6.6. Urine protein/creatinine ratio > 1.0 at screening
7. Inability to complete Quality of Life questionnaires
8. Contraindications for modified radical mastectomy (MRM), including contrast media safety, are as for standard magnetic resonance imaging (MRI)
Recruitment start date
01/11/2008
Recruitment end date
30/12/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Lincoln County Hospital
Lincoln
LN2 2QY
United Kingdom
Funders
Funder type
Industry
Funder name
Roche (UK): Educational grants, drugs supplied
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi Aventis (UK): Educational grants
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Chugai Pharma (UK): Drugs supplied
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary