Comparing ARomatase Inhibition when given with or without SaracaTinib as an Advanced breast CAncer Therapy (ARISTACAT)

ISRCTN	ISRCTN23804370
DOI	https://doi.org/10.1186/ISRCTN23804370
Protocol serial number	Version 1.0
Sponsor	The Common Services Agency (UK)
Funder	AstraZeneca (UK)

Submission date: 29/11/2011
Registration date: 06/01/2012
Last edited: 02/03/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-saracatinib-post-menopausal-women-advanced-breast-cancer-aristacat

Contact information

Prof David Cameron
Scientific

Edinburgh Cancer Centre
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

Study information

Primary study design	Interventional
Study design	Multi-centre placebo-controlled double-blind randomised phase II trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	ARISTACAT
Study objectives	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(s)	National Research Ethics Service, West of Scotland, 6 December 2011, ref: 11/WS/0114
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Anastrazole, exemestane, saracatinib
Primary outcome measure(s)	Current primary outcome measure as of 02/04/2019: Progression free survival will be measured using time to progression through standard, regular, clinical assessment. Previous primary outcome measure: 1. Progression free survival 2. Time to progression will be measured through standard, regular, clinical assessment
Key secondary outcome measure(s)	1. Toxicity 2. Change in tumour size analysed using a Waterfall plot in the two strata separately 3. Overall survival
Completion date	31/03/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	140
Total final enrolment	140
Key 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
Key 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
Date of first enrolment	01/03/2012
Date of final enrolment	31/03/2017

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

Edinburgh Cancer Centre

Edinburgh
EH4 2XU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		02/03/2023	02/03/2023	Yes	No
Basic results		20/03/2019	02/04/2019	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			09/07/2019	No	Yes

Additional files

ISRCTN23804370_BasicResults_20Mar19.pdf: Uploaded 02/04/2019

Editorial Notes

02/03/2023: Publication reference added.
09/07/2019: The following changes were made to the trial record:
1. A link to results was added to the results (plain English) field.
2. The total final enrolment was added.
02/04/2019: The following changes have been made:
1. The basic results of this trial have been uploaded as an additional file.
2. The primary outcome measure was updated.