Response to Optimal Selection of neo-adjuvant Chemotherapy in Operable breast cancer: A randomised phase III, stratified biomarker trial of neo-adjuvant 5-Fluorouracil, Epirubicin and Cyclophosphamide vs Docetaxel and Cyclophosphamide chemotherapy.

Trial Overview and Summary

Chief Investigator: Professor Daniel Rea
Sponsor: University of Birmingham
Funders: Cancer Research UK (CRUK/12/046) and Celgene
Disease Site: Breast Cancer
Trial Type: Clinical Trial of an Investigational Medicinal Product 
Status: Follow Up
UKCRN Study ID: (if applicable) 19069
ISRCTN Number: ISRCTN15094808
Open to new sites? No
Recruitment start date: 07-Oct-2015
Anticipated Recruitment end date 31-May-2023
CRCTU Trial Management Team: Late Phase Trial Management Team - B
Trial E-mail Address:

 Trial Summary 

Chemotherapy given before surgery (neo-adjuvant chemotherapy) for early breast cancer can reduces the amount of surgical treatment required by patients, often avoiding the need for a mastectomy. In addition, assessment of response to neo-adjuvant chemotherapy from inspection of the surgical specimen after treatment gives additional information on prognosis. A pathological complete response (pCR) is generally associated with excellent prognosis and no pCR is associated with poorer outcomes. To maximise pCR, patients are generally treated with both epirubicin and docetaxel containing chemotherapy combinations, increasing toxicity due to exposure to both drugs. Analysis of previous adjuvant chemotherapy trials strongly suggests that a combination of two genetic markers called CEP17 and TOP2A, predict for epirubicin sensitivity. Therefore it may be unnecessary to treat all patients with both epirubicin and docetaxel.
Current standard of care in patients with involved axillary nodes before chemotherapy is an axillary dissection. When there is no residual cancer this becomes an unnecessary procedure. A sentinel lymph node biopsy (SLNB) is a surgical technique which can be used to assess whether there is lymph node involvement. The data on the accuracy of use of SLNB post neo-adjuvant chemotherapy is controversial.
ROSCO has therefore been designed to answer two questions:
  • Is there a role for CEP17/TOP2A testing in selecting which chemotherapy drugs to use as neo-adjuvant chemotherapy for early breast cancer?
  • Is SLNB a reliable test to show that neo-adjuvant chemotherapy has eliminated all the cancer cells within in the axillary lymph nodes?
ROSCO aims to recruit 1056 adult patients with early breast cancer from hospitals around the UK. Patients consenting to the trial are initially registered and their tumour tested centrally for the presence of CEP17 and TOP2A. Patients are then randomised to one of two treatment arms:

Arm A: 4 cycles of anthracycline containing chemotherapy (called FEC) given at 3 weekly intervals
Arm B: 4 cycles of taxane containing chemotherapy (called TC) given at 3 weekly intervals

Patients who test positive for the HER2 receptor will also receive trastuzumab (Herceptin) with their chemotherapy. On completion of 4 cycles of chemotherapy patients will have standard surgery for their breast cancer. Patients with involved nodes may also have a combined SLNB and axillary node dissection.
The response of the tumour to neoadjuvant chemotherapy will be determined. Those patients achieving a pCR may stop treatment. Those patients who do not achieve pCR will cross over to the opposite type of chemotherapy treatment (e.g. those randomised to Arm A will receive Arm B chemotherapy and vice versa).
Patients will be followed up for 5 years.
Please note that the trials team cannot give individual’s clinical advice. Patients and their families should contact their treating physician to discuss trials for which they may be eligible.

Trial Protocol

Please Note:
Clinical trial protocols are complex technical documents which should only be used for the treatment of subjects taking part in the trial. Patients who are interested in taking part in the trial are advised to talk to their health care professional or refer to the CancerHelp website.
Investigators please ensure you have R&D approval for this specific version of the protocol before using as a reference.
The Trial Protocol can be viewed on the following page: ROSCO: For Investigators 

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