Breast cancer MedDRA version: 17.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 5-fluorouracil
Product Code: 5-fluorouracil
Pharmaceutical Form: Infusion
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Current Sponsor code: 5-Fluorouracil
Concentration unit:
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ROSCO Main Trial • Patient with histological diagnosis of invasive breast cancer • Suitable for neo-adjuvant chemotherapy in opinion of investigator • Unifocal tumour: - Radiological size greater than or equal to (=) 20 mm by ultrasound (or in some cases Magnetic Resonance Imaging (MRI) is allowed) - T4 tumour of any size with direct extension to (a) chest wall or (b) skin or both - Inflammatory carcinoma with tumour of any size OR Multifocal tumour: ?- The sum of each tumour’s maximum diameter must be =20 mm (total sum of multifocal deposits =20 mm by ultrasound) OR Other locally advanced disease - Biopsy confirmed axillary lymph node involvement or large or fixed axillary lymph nodes (radiological diameter =20 mm or clinical N2), or ipsilateral supraclavicular nodes and primary breast tumour of any diameter - Involvement of large or fixed axillary lymph nodes (radiological diameter =20 mm or clinical N2), or ipsilateral supraclavicular nodes without a primary breast tumour identified: in this case the presence of breast cancer in a lymph node must be histopathologically confirmed by lymph node biopsy (trucut or whole lymph node) • Patients with bilateral disease are eligible to enter the trial, if one of the criteria above is met for disease in at least one breast • Any HER2 status • Patient fit to receive the trial chemotherapy regimen in the opinion of the responsible clinician. The following recommendations must be taken into account when making this assessment: - Patients with HER2 positive disease must not have clinically significant cardiac abnormalities. Cardiac function should be assessed by physical examination and baseline measurement MUST be made of Left Ventricular Ejection Fraction (LVEF) by Multi Gated Acquisition (MUGA) scan or echocardiogram (ECHO). LVEF must be within the normal range as defined locally by the treating hospital - Patients must have adequate bone marrow, hepatic, renal and haematological function • Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 • Women of child-bearing potential, or men in a relationship with a woman of child-bearing age, prepared to adopt adequate contraceptive measures if sexually active • 18 years or older • Male or female • Written informed consent for the trial • Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy is required • Willing and able to comply with scheduled visits, treatment plan and other study procedures Sentinel Lymph Node Biopsy Study (in addition to above) • Biopsy/fine needle aspiration proven involved ipsilateral axillary lymph nodes at diagnosis Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: ROSCO Main Trial • Tumours of low or intermediate grade (Grade 1 or 2) which are also Oestrogen Receptor (ER) rich and Progesterone Receptor (PgR) rich or PgR unknown, whatever the size or nodal status • Previous invasive breast cancer • Unequivocal evidence of metastatic disease • Previous diagnosis of other malignancy unless: - Disease-free for 5 years; or - Previous basal cell carcinoma, cervical carcinoma in situ, superficial bladder tumour; or - Contralateral or ipsilateral DCIS of the breast treated by surgery alone • Previous chemotherapy • Prior extensive radiotherapy (as judged by the investigator) to bone marrow • Previous neo-adjuvant endocrine therapy (unless less than 6 weeks duration) • Concomitant hormonal therapies/chemotherapy or any other medical treatment in relation to treating the breast cancer • In HER2 positive patients risk factors precluding co-administration of trastuzumab and FEC75 - Previous myocardial infarction during the 6 months prior to recruitment - LVEF below institutional lower limit of normal and no echocardiographic evidence of heamodynamically - Significant valvular heart disease or ventricular contractility • Prior diagnosis of cardiac failure • Uncontrolled hypertension, coronary heart disease other significant cardiac abnormality • Bleeding diathesis • Presence of active uncontrolled infection • Any evidence of other disease which in the opinion of the investigator places the patient at high risk of treatment related complication • Pregnant (female patients of child bearing potential should have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to trial entry) • Lactating females • Any concomitant medical or psychiatric problems which in the opinion of the investigator would prevent completion of treatment or follow-up Sentinel Lymph Node Biopsy Study (in addition to above) • Negative nodes at diagnosis • SLNB at diagnosis • Allergy to patent blue dye
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Complete pathological response (pCR) rate: pCR will be determined at surgery in patients following treatment with neo-adjuvant chemotherapy and will be 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. The number of patients achieving pCR as a proportion of those randomised will be presented.;Main Objective: The objectives of this study are to determine: 1.Is there a role for CEP17 and TOP2A testing in selecting anthracycline or taxane chemotherapy as neo-adjuvant chemotherapy for early breast cancer? 2.Is SLNB post neo-adjuvant chemotherapy in patients with biopsy proven ipsilateral axillary lymph node metastasis at diagnosis sufficiently sensitive to replace routine axillary node clearance? ;Secondary Objective: The primary translational science objective of the ROSCO trial is to validate the use of a predictive biomarker of anthracycline sensitivity for clinical use in neo-adjuvant breast cancer. A secondary exploratory objective will be to use a tissue, Deoxyribonucleic Acid (DNA), and serum/plasma sample repository from consented patients to extend current translational research into candidate biomarkers of chemotherapy response, predictive markers of response to chemotherapy without invasive testing, and pharmacogenomics to investigate potential markers of toxicity. The patient experience during and after chemotherapy is also important to describe in ROSCO. A standard Quality of Life (QoL) evaluation will be performed. Patients will be requested to complete a QoL Booklet at specific time points during and after treatment. ;Timepoint(s) of evaluation of this end point: Following surgical resection | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Following surgical resection 2. On completion of protocol treatment 3. On completion of protocol treatment 4. Following surgical resection 5. Measured on completion of each cycle of chemotherapy 6. Following surgical resection 7. Following surgical resection 8. Measured continually 9. Measured continually 10. Measured continually 11. Measured continually 12. Will be measured at baseline, on completion of 2 and 4 cycles of neo-adjuvant chemotherapy, 6 weeks after completion of surgery and 1 and 2 years post-randomisatiom 13. Measured on completion of each cycle of chemotherapy 14 - 15. Analyses will be performed retrospectively ;Secondary end point(s): 1. pCR rate in breast alone: defined by the number of patients who have no residual invasive carcinoma within the breast (DCIS permitted) as a proportion of those randomised 2. Clinical response in breast alone: defined as the number of patients with complete response (CR) or partial response (PR), measured by callipers at baseline and on completion of treatment, as a proportion of the number of patients randomised. Response will be assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. 3. Radiological response in breast alone: defined as the number of patients with CR or PR, measured by ultrasound (or MRI if used at baseline when ultrasound unavailable) at baseline and on completion of treatment, as a proportion of the number of patients randomised. Response will be assessed using RECIST version 1.1. 4. Rates of breast conservation: defined as the number of patients treated with breast conservation as a proportion of the total number of patients receiving surgery. The number of patients who are assessed as requiring mastectomy prior to chemotherapy and subsequently are down staged to permit a breast conserving final surgical procedure as a proportion of the total number of patients assessed as requiring mastectomy prior to chemotherapy 5. To | — |
Countries
United Kingdom
Contacts
Public ContactDr Sarah Bowden
University fo Birmingham
Outcome results
None listed