NCT01564056

Adjuvant Systemic Treatment for (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment

Adjuvant Systemic Treatment for Oestrogen-receptor (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment. A French UNICANCER Geriatric Oncology Group (GERICO) and Breast Group (UCBG) Multicentre Phase III Trial

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,989 (actual)
• Sponsor: UNICANCER · Academic / Other
• Sex: Female
• Age: 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to evaluate the benefit of adjuvant chemotherapy on overall survival for elderly patients with breast cancer, in a sub group with a high risk of relapse according to Genomic Grade test.

Detailed description

The purpose of this trial is to address the question of the added value of adjuvant chemotherapy on survival in 70+ BC patients with ER+ disease, deemed "at risk of relapse" (pN+ or pN0 with a high prognostic classifier, namely GG by RT-PCR) and planned to receive as well adjuvant endocrine treatment. This benefit will be weighed with the competition exerted by comorbidities on mortality. As in many recently developed trials evaluating specific strategies for the elderly (e.g. CALGB 49907 (8); bevacizumab and colorectal cancer in the PRODIGE 20 elderly program supported by the PHRC 2010), the choice of chemotherapy regimen will be left to the investigator between 3 "standard" ones: TC x 4 (no anthracyclines), AC x 4 or MC x 4 (better cardiac tolerance), in order to obtain enrolment of a less highly selected population, more representative of the general population to the difference of the high selection classically observed in standard oncology trials. In parallel, patients not included in the randomized part (whatever reason) and treated with adjuvant endocrine treatment only will be followed up as a separate observational cohort. 1. Screening All women 70+ having undergone surgery for invasive pN0 or pN+, ER+ HER2- BC, will be screened and invited to participate. Pre-selection will be possible pre-operatively. 2. Prognostic signature After having signed a written informed consent, the prognostic signature Genomic Grade (GG) will be assessed by RT-PCR. 3. Randomization (Group I) Only the patients with a Genomic Grade (GG) considered as high will be randomized (1:1): endocrine treatment only (Arm A) versus endocrine treatment + adjuvant chemotherapy (Arm B). Randomization1:1 between arm A and B will be done using minimization stratified according to pN status (pN+ vs pN0), G8 (≤ vs \> 14), and center. Given (i) the high potential of less cardiotoxic regimen including liposomal formulations for anthracyclines or excluding anthracyclines and (ii) the wish to capture the whole population to depict the heterogeneity of ageing from 70, adjuvant chemotherapy (Arm B) will be left to the choice of investigator amongst 3 standard regimen of same duration, 4 cycles given every 3 weeks + primary prophylactic GCSF: * AC = doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² * TC = docetaxel 75 mg/m² + cyclophosphamide 600 mg/m² * MC = liposomal non pegylated doxorubicin (Myocet) 60 mg/m² + cyclophosphamide 600 mg/m² 4. Patients not randomized (Group II) Patients not randomized for any reason (low GG, randomization refusal or treatment refusal, etc.) will enter a surveillance program and will be able to participate to other specific geriatric studies (GERICO project to evaluate the impact of comprehensive geriatric assessment on quality of life, treatment administered and BC survival after 75 years; EORTC study to validate the scale specifically developed for elderly ELD15). The Group II will present a triple interest and will participate, together with randomized patients, to achieve the following objectives: * validation of the prognostic value of Genomic Grade and performance of the test in the elderly BC population, as compared to standardized routine histopathological parameters, * translational studies to identify molecular signatures, * collection of descriptive data including comorbidities and polymedication. 5. Endocrine treatment and radiotherapy In both Groups (I and II), the endocrine treatment will be left to the choice of the investigator (tamoxifen, aromatase inhibitor or sequential) and radiotherapy will follow standard guidelines.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	HORMONOTHERAPY	Hormonotherapy will be administered during 5 years following chemotherapy when allocated. (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).
DRUG	CHEMOTHERAPY then HORMONOTHERAPY	CHEMOTHERAPY regimen will be chosen amongst the following ones: i) 4 cycles of TC (docetaxel + cyclophosphamide) * Docetaxel 75 mg/m² IV infusion at hospital every 21 days * Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days ii) 4 cycles of AC (doxorubicin + cyclophosphamide) * Doxorubicin 60 mg/m² IV infusion at hospital every 21 days * Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days iii) 4 cycles of MC (liposomal non pegylated doxorubicin \[Myocet®\]+ cyclophosphamide) * Myocet® 60 mg/m² IV infusion at hospital every 21 days * Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Timeline

• Start date: 2012-04-12
• Primary completion: 2022-04-11
• Completion: 2026-03-01
• First posted: 2012-03-27
• Last updated: 2025-06-26

Locations

84 sites across 2 countries: Belgium, France