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 |
| Secondary identifying numbers | Version 1.0 |
- 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
Contact information
Prof David Cameron
Scientific
Scientific
Edinburgh Cancer Centre
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Study information
| Study design | Multi-centre placebo-controlled double-blind randomised phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Anastrazole, exemestane, saracatinib |
| Primary outcome measure | 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 |
| Secondary outcome measures | 1. Toxicity 2. Change in tumour size analysed using a Waterfall plot in the two strata separately 3. Overall survival |
| Overall study start date | 01/03/2012 |
| Completion date | 31/03/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 140 patients will be recruited over a 2 year period at around 20 sites in the UK |
| 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
- Scotland
- United Kingdom
Study participating centre
Edinburgh Cancer Centre
Edinburgh
EH4 2XU
United Kingdom
EH4 2XU
United Kingdom
Sponsor information
The Common Services Agency (UK)
Government
Government
c/o Ms Eve Macdonald
Gyle Square
1 South Gyle Crescent
Edinburgh
EH12 9EB
United Kingdom
| Phone | +44 (0)131 275 7058 |
|---|---|
| eve.macdonald@nhs.net | |
| Website | http://www.nhsnss.org/ |
"ROR" |
https://ror.org/04za2st18 |
Funders
Funder type
Industry
AstraZeneca (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 20/03/2019 | 02/04/2019 | No | No | |
| Plain English results | 09/07/2019 | No | Yes | ||
| Results article | 02/03/2023 | 02/03/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
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.
