Avastin® Randomised Trial with neo-adjuvant chemotherapy for patients with early breast cancer

ISRCTN	ISRCTN68502941
DOI	https://doi.org/10.1186/ISRCTN68502941
ClinicalTrials.gov (NCT)	NCT01093235
Clinical Trials Information System (CTIS)	2008-002322-11
Protocol serial number	N/A
Sponsor	Cambridge University Hospitals NHS Foundation Trust (UK)
Funders	Cancer Research UK (CRUK) (UK) - Clinical Trials Advisory and Awards Committee (CTAAC), Roche (UK), Sanofi-Aventis (UK)

Submission date: 03/02/2009
Registration date: 17/03/2009
Last edited: 26/10/2022

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/trial-giving-bevacizumab-avastin-chemotherapy-before-surgery-early-her2-negative-breast-cancer-artemis

Contact information

Dr Helena Earl
Scientific

Addenbrookes Hospital
Oncology Department, Box 193
Cambridge
CB2 0QQ
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised (1:1) multicentre phase III prospective open-label trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised multicentre phase III prospective open-label trial of pre-operative bevacizumab (Avastin®) in combination with neo-adjuvant chemotherapy for early breast cancer patients
Study acronym	ARTemis
Study objectives	A short course of pre-operative bevacizumab (Avastin®) in combination with chemotherapy will improve the pathological complete response to neoadjuvant treatment for HER2-negative breast cancer patients, and thereby improve their chances of breast conservation, as well as improving disease-free and overall survival.
Ethics approval(s)	South East Research Ethics Committee (REC), 19/11/2008, ref: 08/H1102/104
Health condition(s) or problem(s) studied	Early breast cancer
Intervention	Arm A: Docetaxel (D) 100 mg/m^2 intravenous (IV) x 3 cycles every 3 weeks (q3w) followed by 5-fluorouracil 500 mg/m^2 IV, epirubicin 100 mg/m^2 IV and cyclophosphamide 500 mg/m^2 (FEC) on day 1 x 3 cycles q3w Arm B: Docetaxel (D) 100 mg/m^2 IV x 3 cycles every 3 weeks [q3w] and bevacizumab (Avastin®) 15 mg/kg q3w x 3 cycles followed by FEC plus bevacizumab 15 mg/kg x 1 cycle and three weeks later FEC x 2 cycles q3w Duration of treatments is 18 weeks. Duration of follow-up is 5 years.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Bevacizumab (Avastin®), docetaxel, 5-fluorouracil, epirubicin, cyclophosphamide
Primary outcome measure(s)	Complete pathological response (pathCR) rates (tumour and lymph nodes) after neoadjuvant chemotherapy defined as no residual invasive carcinoma within the breast (ductal carcinoma in situ [DCIS] permitted) and no evidence of metastatic disease within the lymph nodes, to be measured at surgery.
Key secondary outcome measure(s)	1. Disease-free survival, to be measured through follow-up 2. Overall survival, to be measured through follow-up 3. PathCR rate in breast alone, to be measured at surgery 4. Radiological response after 3 and after 6 cycles of chemotherapy 5. Rate of breast conservation, to be measured at surgery 6. Toxicities including in particular cardiac safety and surgical complications (wound healing, bleeding, and thrombosis), to be measured during treatment and follow-up
Completion date	31/01/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	800
Total final enrolment	800
Key inclusion criteria	1. Patients (aged 18 to 70 years [no age limit but must be fit enough to received chemotherapy], either sex) with histologically confirmed HER2-negative invasive breast cancer (either IHC 0/1 or IHC 2+ and fluorescence in situ hybridisation [FISH] negative) 2. T2 tumours and above (maximum tumour diameter greater than or equal to 20 mm from an ultrasound) and T4 tumours (including inflammatory breast cancer). For multi-focal tumours, the sum of each tumour's maximum diameter must be greater than or equal to 20 mm, and will be designated 'total tumour size'. 3. Any T stage with large axillary nodes (greater than 20 mm) and/or fixed axillary nodes (clinical N2) 4. Suitable for neoadjuvant chemotherapy in the opinion of the responsible clinician
Key exclusion criteria	1. HER2 positive invasive cancer (IHC 3+ or FISH positive) 2. Uni-focal T0 and T1 tumours with no fixed axillary node or no node greater than or equal to 20 mm (multifocal tumours where the total tumour size [sum of maximum diameter of each lesion] is greater than or equal to 20 mm can be included - see above) 3. Patient not suitable for neoadjuvant chemotherapy in opinion of responsible clinician 4. Evidence of metastatic disease 5. Prior endocrine therapy 6. Prior history of breast cancer 7. Prior diagnosis of ischaemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thrombo-embolic disease, cardiac failure, inflammatory bowel disease, gastro-duodenal ulcer, symptomatic diverticulitis, or bleeding diathesis 8. Uncontrolled hypertension
Date of first enrolment	01/04/2009
Date of final enrolment	31/01/2013

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Addenbrookes Hospital

Cambridge
CB2 0QQ
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	results	01/06/2015		Yes	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			26/10/2022	No	Yes

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.