Evaluating a Personalized Treatment Strategy for Young Women with Early Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-01-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Horizon Europe - Grant Agreement N°101156800

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate that the strategy using gene expression (Prosigna®)-driven decision to administer adjuvant CT or not is non-inferior to the standard of care (adjuvant CT) in premenopausal women with HR-positive/HER2-negative primary BC treated with optimal ET in terms of invasive breast cancer free survival (IBCFS), on the global population*.

Secondary objectives 8

1. To demonstrate that, in the global population* with tumours for which the Prosigna® score is below the cut-off (≤60) for chemotherapy use (approximately 70% of the total), ET including OFS alone is non-inferior to CT plus ET with respect to IBCFS
2. To compare the efficacy of Prosigna®-driven treatment against standard clinical practice in the global population* on Distant recurrence-free interval (DRFI), Distant recurrence-free survival (DRFS), Breast cancer-specific survival (BCSS) and Overall survival (OS)
3. To compare the efficacy, on the population with tumours for which the Prosigna® score is ≤60 for chemotherapy use (approximately 70% of the total), of ET including OFS alone and CT-ET on DRFI, DRFS BCSS and OS
4. To evaluate the impact of Prosigna®-driven treatment against standard clinical practice in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60 on multiple Overall QoL, physical and psychosocial symptoms and breast cancer frequent symptoms/side effects.
5. To evaluate the impact of Prosigna®-driven treatment against standard clinical practice in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60 on health and safety osteoporosis, cardiovascular disease, fertility) and health behaviors (physical activities, tabacco and alcohol consumption, adherence to ET) over the course of the study
6. To evaluate communication, uncertainties and concerns related to de-escalation non-inferiority trials in OPTIMA-YOUNG population*
7. To establish the cost-effectiveness of Prosigna®-driven treatment compared to standard clinical practice in the patients recruited in France, Italy, Spain for the OPTIMA-YOUNG trial and United Kingdom for OPTIMA, including assessing the impact on direct healthcare costs, indirect costs and Quality-Adjusted Life Years based on the EuroQOL-5D-5L (EQ-5D-5L) questionnaire.
8. To evalute the perceived ease of use of digital platform (SUS) for research WeShare in the OPTIMA-YOUNG population*

Conditions and MedDRA coding

Premenopausal patients with high-risk HR-positive/HER2-negative breast cancer (BC) defined by tumour size and axillary lymph node status. One of the following must apply: a. 1-3 lymph nodes involved AND any invasive tumour size. b. node negative (including micrometastases in at least 1 node [i.e. deposit >0.2-2mm diameter]) AND invasive tumour size ≥ 50mm.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient’s consent;
2. Premenopausal defined by patient that are not post-menopaused
3. Female
4. Age ≥ 35 years
5. Diagnosis of invasive HR-positive (ER≥10% of tumour cells stained positive and any PR expression) HER2-negative (IHC score 0-1+ or 2+ with negative/non-amplified ISH) invasive breast cancer; ER and HER2 determination will be assessed according to latest ASCO/CAP or national guidelines (Kimberly H. Allison et al. 2020);
6. Breast and axillary surgery completed ≤ 12 weeks from study entry and randomization;
7. Availability of a Formalin-Fixed Paraffin-Embedded (FFPE) tumour sample from surgery to perform Prosigna® analysis or slides.
8. Tumour size and axillary lymph node status. One of the following must apply: a. 1-3 lymph nodes involved AND any invasive tumour size. b. node negative (including micrometastases in at least 1 node [i.e. deposit >0.2-2mm diameter]) AND invasive tumour size ≥ 50mm.
9. Multiple ipsilateral breast cancers are permitted provided that at least one tumour meets the tumour size and axillary lymph node entry criteria, and none meet any of the exclusion criteria.
10. Bilateral breast cancers are permitted provided the tumour(s) in one breast meets the eligibility criteria and the other, contralateral tumour is not ER negative and/or HER2 positive and not clinically significant, defined by both of the following: a. The contralateral tumour does not fulfil the tumour size and lymph node eligibility criteria required for trial entry; i.e. the following are not acceptable: i. presence of lymph node macro-metastases; ii. tumour size ≥50mm when there is no lymph node involvement. b. The treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy.
11. Fitness to receive adjuvant chemotherapy, as judged by the treating physician;
12. Short term pre-surgical treatment with endocrine therapy, including in combination with non-cytotoxic agents, is allowed providing that the duration of treatment did not exceed 8 weeks;
13. Patients affiliated with or a benifiting from the local social security system, health social security system, or other local regulatory requirements
14. Patients must agree to use adequate contraception methods for the duration of study treatment and for the duration specified in the SmPC after completing the treatment, unless agreed with the treatment physician the safety of attempt a pregnancy, which could be possible after at least 18 months of endocrine therapy.

Exclusion criteria 9

1. Postmenopausal women. Women who fulfil the following criteria at trial entry will be considered postmenopausal: a. Age >45 and natural amenorrhoea of at least 1 year’s duration. b. Bilateral surgical oophorectomy. c. For amenorrhoea not fulfilling the above criteria the diagnosis of postmenopausal status should be supported by hormone measurement: FSH levels must be > 25IU/L with low oestradiol (i.e. within the locally defined postmenopausal range), in the event of doubt measured on 2 occasions preferably 4-6 weeks apart. This applies to women who have undergone hysterectomy without bilateral surgical oophorectomy and are age <60; those ≥60 may be considered postmenopausal.
2. Stage IV breast cancer;
3. Start of adjuvant systemic treatment (except for neoadjuvant endocrine therapy for a duration ≤ 8 weeks) before trial entry*;
4. Previous diagnosis of malignancy except: a. Previous ductal carcinoma in situ (DCIS) or pleomorphic lobular carcinoma in situ (LCIS) of the breast managed by local treatment only; b. Previous in situ carcinoma as defined by the International Classification of Diseases for Oncology (ICD-O) including basal cell carcinoma of skin and cervical intraepithelial neoplasia; c. Previous invasive malignancy managed by local treatment only AND disease-free for at least 10 years.
5. Patients enrolled in another interventional therapeutic trial within 30 days of inclusion;
6. Presence of concomitant medical and/or psychiatric comorbidities and/or social problems that might prevent informed consent, treatment compliance or follow up;
7. Person deprived of their liberty or under protective custody or guardianship.
8. Pregnant women or women who are breast-feeding at inclusion.
9. Patients unwilling or unable to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures because of geographic, familial, social, or psychological reasons.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Invasive Breast Cancer Free Survival (IBCFS) in the global population, defined according to the STEEP version 2.0 system (Tolaney et al., JCO 2021) as the time from the date of randomization to the date of the first event of ipsilateral loco-regional invasive breast cancer recurrence, distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause.

Secondary endpoints 8

1. Same as primary enpoint but restricted to with tumours for which the Prosigna® score is below the cut-off (≤60) for chemotherapy use (approximately 70% of the total).
2. According to the STEEP version 2.0 system definition, in the global population : Distant recurrence free interval (DRFI), Distant recurrence free survival (DRFS), Breast cancer specific survival (BCSS)
3. According to the STEEP version 2.0 system definition, in the global population with tumours for which the Prosigna® score is ≤60 : Distant recurrence free interval (DRFI), Distant recurrence free survival (DRFS), Breast cancer specific survival (BCSS), Overall survival (OS)
4. QoL, physical and psychosocial symptoms and breast cancer frequent symptoms/side effects will be assessed in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60 using the following questionnaires: Quality of life (EORTC QLQ-C30 and BR42), Anxiety and Depression (GAD-7 and PHQ8), Cognition (FACT Cog), NCCN Distress thermometer, Return to work
5. Health and safety outcomes: osteoporosis (Number non-traumatic fractures), cardiovascular disease (Number of major cardiovascular events, including stroke, MI, heart failure, cardiovascular deaths), fertility (Number of pregnancies) and health behaviour : physical Activity Levels (IPAQ), BMI, tobacco and alcohol consumption Self-reported adherence to ET (VOILS) in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60
6. Communication aspects, uncertainties and fears related to participating in a de-escalation trial will be assessed using the following questionnaires : Fear of Cancer Recurrence (FCRI-SF), Motivation to enter the trial (SPECIFIC), Recall and expectation on potential treatment related toxicities (ad hoc questionnaire), Decision Conflict (SURE), Decision Regret Scale (DRS) in the OPTIMA-YOUNG population*.
7. Cost-effectiveness analysis of Prosigna®-driven treatment compared to standard clinical practice, summarised as the incremental cost-effectiveness ratio in the patients recruited in France, Italy, Spain for the OPTIMA-YOUNG trial and United Kingdom for OPTIMA.
8. Score of perceived ease of use (SUS) of the digital platform (WeShare) for research on the OPTIMA-YOUNG population*.

Investigational products

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

Test 15

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

7 EU/EEA countries · 107 investigational sites

By country

Investigational sites

Results and documents

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

Documents 116 files

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

Application history

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