Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Version 1.0
Study information
Scientific title
Comparing ARomatase Inhibition when given with or without SaracaTinib as an Advanced breast CAncer Therapy (ARISTACAT): a randomised phase II study of aromatase inhibitionwith or without the src-inhibitor AZD0530 in post-menopausal women with advanced breast cancer
Acronym
ARISTACAT
Study hypothesis
1. Comparison of progression free survival between cohort receiving aromatase inhibition plus saracatinib, versus those receiving aromatase inhibition plus placebo
2. Toxicity, response rate and overall survival.
Translational sub-studies are also planned
Ethics approval
National Research Ethics Service, West of Scotland, 6 December 2011, ref: 11/WS/0114
Study design
Multi-centre placebo-controlled double-blind randomised phase II trial
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 contact details below to request a patient information sheet
Condition
Advanced Breast Cancer
Intervention
The patients will be allocated to a treatment using a minimisation algorithm. Stratification factors will be:
1. AI sensitivity strata
2. Disease site (bone metastases alone versus any other sites
3. Bisphosphonate use
4. Performance status (0 v 1 v 2)
5. Treatment centre
Patients will be enrolled into one of two strata:
1. AI-sensitive/ naïve
These patients with have potentially AI-sensitive tumours
Treatment = anastrazole 1mg daily + saracatinib 175 mg daily OR exemestane 25mg daily + saracatinib 175 mg daily
2. Prior-AI
These patients will have cancers which have already progressed on an AI, but for whom there is likely to still be some endocrine sensitivity
Treatment = anastrazole 1mg daily + placebo daily OR exemestane 25mg daily + placebo daily
Saracatinib (AZD0530) is an oral src inhibitor and can be administered with or without food. The choice of either anastrazole or exemestane is driven by what would be an acceptable standard therapy for the patient, and then the patients are randomised to either get saracatinib or placebo.
Intervention type
Drug
Phase
Phase II
Drug names
Anastrazole, exemestane, saracatinib
Primary outcome measure
1. Progression free survival
2. Time to progression will be measured through standard, regular, clinical assessment
Secondary outcome measures
1. Toxicity
2. Change in tumour size analysed using a Waterfall plot in the two strata separately
3. Overall survival
Overall trial start date
01/03/2012
Overall trial end date
31/03/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Females who are clearly post menopausal with Estrogen Receptor (ER) positive (Allred score ≥ 3) advanced breast cancer with at least one lesion which is measurable. They may also have additional evaluable but non-measurable lesions.
2. Patients must be performance status 0 2
3. Suitable for treatment with an aromatase inhibitor
4. Life expectancy > 3 months
5. Cancer must be HER2- (by FISH and/or IHC as appropriate), OR if the cancer is HER2+ the patient must not be a candidate for ant-HER2 therapy
6. All patients will need to also meet inclusion criteria for one of the two main strata:
6.1. AI-sensitive/naive group either never previously treated with an aromatase inhibitor, but if treated with tamoxifen must not have rapid progression on tamoxifen (i.e. treated for at least 24 months adjuvant or ≥ 6 months in metastatic setting); or, if previously treated with an AI, only in the adjuvant or neo-adjuvant setting AND have remained free of progression for at least 12 months whilst not being treated with an AI
6.2. Prior AI group patients NOT meeting the criteria in 6.1 (above), but previously treated with a non-steroidal AI without progression for at least 24 months in the (neo-) adjuvant setting or for at least 6 months for advanced disease
7. Patients who have had two lines of prior AI therapy will not be eligible UNLESS they were switched from one AI to another ONLY for reasons of toxicity, and ONLY during (neo-) adjuvant therapy AND in the absence of any evidence of progression/relapse
8. Single site of bone disease must be histologically confirmed and known not to be ER negative
9. Palliative radiotherapy can be given to bone lesions within 4 weeks of trial entry provided not more than 20% of the bone marrow is irradiated, AND there is at least one other measurable bone lesion which has clearly progressed since any prior irradiation
10. Haematology commensurate with a phase II hormonal therapy study: Neutrophils > 1.5 * 109/l, Hb> 10.0 g/dl and Platelets > 100 * 109/l
11. Biochemistry similar: albumin normal, ALT/AST < 2.5 ULN, Alk Phos < 5 * ULN unless of bone origin, e-GFR > 50ml/min
12. Normal urea & electrolytes
13. Patients receiving bisphosphonates are eligible, provided they are commenced before, or at, trial entry
14. Patients will be stratified by use of, or stated intention to give, bisphosphonate at randomisation
15. Patients ideally should have been on therapy for at least 1 week before starting trial therapy, but must start within 1 week after starting trial therapy
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
140 patients will be recruited over a 2 year period at around 20 sites in the UK
Participant exclusion criteria
1. Patients with short life expectancy or significant other co-morbidity including pulmonary fibrosis
2. Rapidly progressive visceral disease (lymphangitis, diffuse liver disease, uncontrolled CNS disease)
3. Resting ECG with a measureable QTc >480 msec
4. Any evidence of severe or uncontrolled systemic conditions (e.g. interstitial lung disease [bilateral, diffuse, parenchymal change])
5. Life expectancy < 3 months
6. Contra-indication to either AZD0530 (or excipients) or aromatase inhibition
7. Concomitant chemotherapy or anti-HER2 therapy
Recruitment start date
01/03/2012
Recruitment end date
31/03/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Edinburgh Cancer Centre
Edinburgh
EH4 2XU
United Kingdom
Sponsor information
Organisation
The Common Services Agency (UK)
Sponsor details
c/o Ms Eve Macdonald
Gyle Square
1 South Gyle Crescent
Edinburgh
EH12 9EB
United Kingdom
+44 (0)131 275 7058
eve.macdonald@nhs.net
Sponsor type
Government
Website
Funders
Funder type
Industry
Funder name
AstraZeneca (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
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
Basic results (scientific)
Publication list