Chemotherapy or chemotherapy + hormonotherapy in women over 70 with HER2 receptor-negative but estrogen receptor-positive breast cancer according to their genomic grade

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Apr 2012 → ongoing

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Programme Hospitalier de Recherche Clinique (PHRC), Laboratoire AMGEN et Laboratoire CEPHALON/TEVA

External identifiers

EU CT number

2024-516996-34-00

EudraCT number

2011-004744-22

ClinicalTrials.gov

NCT01564056

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacoeconomic, Therapy

Evaluation of the benefit of adjuvant chemotherapy on overall survival (OS) in the sub group of elderly patients with a high risk of relapse according to Genomic Grade (GG).

Secondary objectives 16

1. Overall survival (OS) taking into account competing causes for mortality (e.g. cormorbidities, functional status, nutritional status).
2. Breast cancer-specific survival (BCSS) and non specific survival
3. Health-related quality of life (QLQ C30 and specific elderly scale QLQ-ELD15);
4. Invasive disease-free survival (iDFS) and distant DFS (dDFS)
5. Event-free survival (EFS)
6. Relapse-free survival (RFS) and distant RFS (dRFS)
7. Toxicity (NCI-CTC V4.0).
8. Geriatric assessment; G8 validation in a specific elderly breast cancer population
9. Prospective validation of a score of 4-year mortality and of its French version in an elderly cancer population.
10. Q-TWiST analysis
11. To evaluate treatment acceptability (willingness test questionnaire).
12. Prognostic value of GG by RT-PCR and performance of the test in the elderly BC population, as compared to standardized routine histopathological criteria (pN, histological grade, mitotic count, Ki67 index).
13. Cost-effectiveness analysis to assess the medico-economic impact of the introduction of adjuvant chemotherapy for women over 70 with a high risk of relapse according to GG.
14. Follow-up of a cohort of elderly BC patients not treated with adjuvant chemotherapy (including non eligibility due to GG).
15. Frozen, formalin-fixed tumor and frozen serum and blood banking will be prospectively performed for future translational studies in both genomics and proteomics (transcriptome and proteome analyses, tissue array analyses).
16. Ancillary study objective (Applicable only for France): - Prognostic value of GG testing on iDFS and D-DFS/D-RFS will be evaluated for the first 500 patients included in the screened population (cohort group and randomized group [in both arms]) with a follow-up of 36 months (the analysis will be performed without unblinding of the treatment)

Conditions and MedDRA coding

oestrogen-receptor (ER)-positive HER2-negative breast carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Women aged ≥ 70 yo,
2. Histologically proven invasive breast cancer (regardless of the type),
3. Complete surgery performed before enrolment: radical modified mastectomy or breast conservative surgery, with either a sentinel lymph node procedure or axillary lymph node dissection
4. Any N status (pN+ or pN0),
5. No clinically or radiologically detectable metastases (M0),
6. Oestrogen receptor (ER)-positive, as defined by a ≥ 10% tumor stained cells by immunohistochemistry (IHC),
7. HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative),
8. Normal haematological function prior to GG evaluation : ANC ≥ 1,500/mm3; platelets count ≥ 100,000/mm3; haemoglobin > 9 g/dl,
9. Normal hepatic function prior to GG evaluation: total bilirubin ≤ 1.25 ULN; ASAT and ALAT ≤ 1.5 ULN; alkaline phosphatases ≤ 3 ULN
10. Creatinine clearance prior to GG evaluation (MDRD formula) ≥ 40 mL/min,
11. PS (ECOG) ≤ 2,
12. Patient able to comply with the protocol,
13. Patients must have signed a written informed consent form prior to any study specific procedures, including the agreement for the use of archived tumoral material for genomic screening and data collection
14. Patients must be affiliated to a Social Health Insurance.

Exclusion criteria 9

1. Any metastatic impairment,
2. Any tumor ≥ T4a (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer),
3. ER-negative breast cancer (i.e. <10% tumor stained cells by IHC),
4. HER2 overexpression, defined as IHC score 3+ or score 2+ and FISH/SISH/CISH positive
5. Any chemotherapy, hormonal therapy or radiotherapy for the current breast cancer before surgery,
6. PS (ECOG) ≥ 3,
7. Any specific contra-indication to the study drugs (including but not limited to hypersensitivity to the study drugs or their components),
8. Patient deprived of freedom or under tutelage,
9. Patient unable to comply with the required medical follow-up for geographic, social or psychological reasons.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS) with 4 years of follow-up (ie median follow-up = 4 years)

Secondary endpoints 14

1. Breast cancer-specific survival (BCSS)
2. Invasive disease-free survival (iDFS)
3. Event-free survival (EFS)
4. Relapse-free survival (RFS)
5. Evaluation of Toxicity
6. Quality of life: Quality of life (QoL) will be assessed using the national version of EORTC QLQ-C30 (version 3) and QLQ-ELD15, a QLQ C30 supplement module for the assessment of quality of life in the elderly patient with cancer
7. Q-TWiST analysis
8. Geriatric assessment
9. Treatment acceptability
10. Predictive value of a 4-year mortality score
11. Usefulness of GG by RT-PCR as a prognostic signature and performance in an elderly population by comparison to standardized routine histopathological criteria and to the results obtained in the general non elderly population
12. Cost-effectiveness analysis
13. Follow-up of a cohort of elderly BC patients not treated with adjuvant chemotherapy (including non eligibility due to GG).
14. Ancillary study criterai (Only applicable for France): The prognostic value of HalioDx GG testing on iDFS and D-DFS/D-RFS will be assessed in the first 500 patients in the screened population (cohort group and randomized group [in both arms]) with a follow-up of 36 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

2 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications