Response to optimal selection of neo-adjuvant chemotherapy in operable breast cancer

Phase 3

• Conditions: Breast cancer; Cancer

• Registration Number: ISRCTN15094808
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-03
• Last Update Posted: 15 May 2023
• Study Completion: 2028-05-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 1050

Inclusion Criteria

1. Patient with histological diagnosis of invasive breast cancer
2. Suitable for neo­adjuvant chemotherapy in opinion of investigator
3. Unifocal tumour: - Radiological size greater than or equal to (=) 20 mm by ultrasound (or in some cases Magnetic Resonance Imaging (MRI) is allowed)
4. T4 tumour of any size with direct extension to:
4.1. Chest wall
4.2. Skin
4.3. Both chest wall and skin
5. Inflammatory carcinoma with tumour of any size OR
6. Multifocal tumour: The sum of each tumour’s maximum diameter must be =20 mm (total sum of multifocal deposits =20 mm by ultrasound) OR
7. Other locally advanced disease:
7.1. 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
7.2. ­ 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)
8. 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
9. Any HER2 status
10. 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
11. Eastern Co­operative Oncology Group (ECOG) performance status of 0 or 1
12. Women of child­bearing potential, or men in a relationship with a woman of child­bearing age, prepared to adopt adequate contraceptive measures if sexually active
13. 18 years or older
14. Male or female
15. Written informed consent for the trial
16. Availability of embedded paraffin tumour blocks from pre­chemotherapy biopsy is required
17. Willing and able to comply with scheduled visits, treatment plan and other study procedures
Sentinel Lymph Node Biopsy Study (in addition to above)
18. Biopsy/fine needle aspiration proven involved ipsilateral axillary lymph nodes at diagnosis

Exclusion Criteria

1. 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
2. Previous invasive breast cancer
3. Unequivocal evidence of metastatic disease
4. Previous diagnosis of other malignancy unless:
4.1. Disease­ free for 5 years OR
4.2. Previous basal cell carcinoma, cervical carcinoma in situ, superficial bladder tumour OR
4.3. Contralateral or ipsilateral DCIS of the breast treated by surgery alone
5. Previous chemotherapy
6. Prior extensive radiotherapy (as judged by the investigator) to bone marrow
7. Previous neo­adjuvant endocrine therapy (unless less than 6 weeks duration)
8. Concomitant hormonal therapies/chemotherapy or any other medical treatment in relation to treating the breast cancer
9. In HER2 positive patients risk factors precluding co­administration of trastuzumab and FEC75
9.1. Previous myocardial infarction during the 6 months prior to recruitment
9.2 LVEF below institutional lower limit of normal and no echocardiographic evidence of haemodynamically
9.3 Significant valvular heart disease or ventricular contractility
10. Prior diagnosis of cardiac failure
11. Uncontrolled hypertension, coronary heart disease other significant cardiac abnormality
12. Bleeding diathesis
13. Presence of active uncontrolled infection
14. Any evidence of other disease which in the opinion of the investigator places the patient at high risk of treatment-related complication
15. Pregnant (female patients of childbearing potential should have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to trial entry)
16. Lactating females
17. Any concomitant medical or psychiatric problems which in the opinion of the investigator would prevent completion of treatment or follow­up
18. Sentinel Lymph Node Biopsy Study (in addition to above)
19. Negative nodes at diagnosis
19. SLNB at diagnosis
20. Allergy to patent blue dye

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Complete pathological response (pCR) rate; Timepoint(s): On completion of 4 cycles of NAC