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| [ Print-friendly version ] |
| Comparing ARomatase Inhibition when given with or without SaracaTinib as an Advanced breast CAncer Therapy (ARISTACAT) |
| ISRCTN | ISRCTN23804370 |
| ClinicalTrials.gov identifier | |
| Public title | Comparing ARomatase Inhibition when given with or without SaracaTinib as an Advanced breast CAncer Therapy (ARISTACAT) |
| 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 |
| Serial number at source | Version 1.0 |
| 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 |
| Lay summary | Lay summary under review |
| Ethics approval |
National Research Ethics Service, West of Scotland, 6 December 2011, ref: 11/WS/0114
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| Study design | Multi-centre placebo-controlled double-blind randomised phase II trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Advanced Breast Cancer |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/03/2012 |
| Anticipated end date | 31/03/2017 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 140 patients will be recruited over a 2 year period at around 20 sites in the UK |
| Interventions |
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. |
| Primary outcome measure(s) |
1. Progression free survival
2. Time to progression will be measured through standard, regular, clinical assessment |
| Secondary outcome measure(s) |
1. Toxicity
2. Change in tumour size analysed using a Waterfall plot in the two strata separately 3. Overall survival |
| Sources of funding | AstraZeneca (UK) |
| Trial website | |
| Publications | |
| Contact name | Prof David Cameron |
| Address |
Edinburgh Cancer Centre
Western General Hospital Crewe Road South |
| City/town | Edinburgh |
| Zip/Postcode | EH4 2XU |
| Country | United Kingdom |
| Sponsor | The Common Services Agency (UK) |
| Address |
c/o Ms Eve Macdonald
Gyle Square 1 South Gyle Crescent |
| City/town | Edinburgh |
| Zip/Postcode | EH12 9EB |
| Country | United Kingdom |
| Tel | +44 (0)131 275 7058 |
| Fax | +44 (0)131 275 7512 |
| eve.macdonald@nhs.net | |
| Sponsor website: | http://www.nhsnss.org/ |
| Date applied | 29/11/2011 |
| Last edited | 06/01/2012 |
| Date ISRCTN assigned | 06/01/2012 |
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| © 2012 ISRCTN unless otherwise stated. | |
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