English Summary - ICE II
An investigational randomized phase II-(III) study on epirubicin plus cyclophosphamide (or CMF) vs. nab-paclitaxel plus capecitabine as adjuvant chemotherapy for elderly non frail patients with an increased risk for relapse of a primary carcinoma of the breast.
Current Status
Trial Design
Multicentre, open, randomized, phase II-(III) trial
Treatment
Patients will be randomized to receive either
• 4 cycles of chemotherapy with epirubicin plus cyclophosphamide (EC) on day 1 q22 or 6 cycles CMF on days 1 and 8 q29
or
• 6 cycles of weekly nab-Paclitaxel 100 mg/m2 on days 1, 8, 15 q22 with a week of rest every 6 weeks in combination with capecitabine 2000 mg/m2, days 1 - 14 orally, divided into 2 daily doses every 3 weeks for 6 cycles.
Patient Population
1. Written informed consent for all study procedures must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
2. Complete baseline documentation must be sent to GBG Forschungs GmbH.
3. Histological confirmed unilateral or bilateral primary carcinoma of the breast.
4. Female and male breast cancer patients with age at first histologically diagnosis and axilla dissection ≥ 65 years.
5. Adequate surgical treatment with complete resection (R0) of the tumor and ≥ 10 axillary nodes. Sole sentinel node biopsy is allowed if the sentinel node shows no tumor involvement.
6. No evidence for distant metastasis at bone scan, liver ultrasound and chest x-ray.
7. Patients with stage pT3/4 or pN2/3 (≥ 4 involved lymph nodes) irrespective of additional risk factors.
8. Patients with stage pT1/2 and pN0/1 (0-3 involved lymph nodes) with an increased risk according to the clinico-pathological or uPA/PAI-1 criteria.
9. ECOG Performance Status ≤ 2.
10. Charlson Scale ≤ 2.
11. Estimated life expectancy of at least 5 years (irrespective of breast cancer diagnosis).
12. The patient must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or a Co- investigator’s site.
Primary Objectives
Phase II:
To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX).
Phase III:
To compare the disease-free survival with epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX).
Secondary Objectives
Phase II:
1. To compare the disease-free survival (DFS) and distant disease free survival (DDFS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in com-bination with capecitabine (PX).
2. To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
3. To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
4. To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
5. To compare a geriatric assessment by Charlson versus VES-13 score or other method depending on ICE I evaluation.
Phase III:
1. To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX).
2. To compare the distant disease free survival with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX).
3. To compare the overall survival with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX).
4. To analyse the efficacy of treatments in subgroups according to clinical stratification factors.
5. To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect to compare a geriatric assessment by Charlson versus VES 13 score
Primary Endpoints
Any local invasive or distant relapse of breast cancer, any contralateral breast cancer, any secondary malignancy (non breast) and any death irrespective of its cause.
Addenda
Final Protocol Version 1, 11.07.2008
Study Report
Although approximately 50% of new diagnosis breast cancers are in patients above the age of 65, elderly people remain substantially under- represented in clinical trials, and therefore are under-treated. A recent trial of the CALBG in patients ≥ 65 years with medium risk of breast cancer demonstrated an improved disease-free and overall survival for those treated with AC or CMF compared to those treated with capecitabine alone. The primary aim of the ICE II trial is to determine the compliance and toxicity of epirubicin plus cyclophosphamide (EC) or CMF versus nab-paclitaxel plus capecitabine as adjuvant therapy in non frail elderly patients.
- Study Group: German Breast Group (GBG)
- Sponsor: GBG Forschungs GmbH
- Study Chair: Prof. Dr. Gunter von Minckwitz
- Clinical Project Management: Horst Mochnatzki
- Data Management / Biometry: Dr. Valentina Nekljudova
- Enrollment Phase II: QII 2009 until QI 2010
- Enrollment Phase III: QI 2010 until QI 2012
- Proposed accrual Phase II: 400
- Proposed accrual Phase II:1058