Deescalation of Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk

NCT05297617 | Recruiting Phase 2

• 3 other identifiers: UC-BCG-21032021-002889-412024-514480-26-00
• Study Type: interventional
• Target: 696
• Locations: 1 country
• Sites: 2

Brief Summary

Hormone therapy is recommended for five years in all patients with hormone receptor-positive breast cancer, but there is no consensus on its duration in low-risk tumours and especially in postmenopausal women. Adjuvant endocrine therapy (ET) is associated with substantial side effects and long-term decreased quality of life. Moreover, while it has been shown that ET provides a real benefit in reducing the relapse rate over time, the deterioration in quality of life may also have a negative effect on patient adherence to treatment. It is therefore important to offer treatment to women with low-risk cancer less intensive treatment strategies. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. The 5-year duration appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Distant relapse-free interval (DRFI)

  Distant relapse-free interval (DRFI) is defined as the time from date of beginning of hormonotherapy to the date of first event of distant recurrence or breast cancer related death

  From date of beginning of hormonotherapy to onset of metastases or death, up to 5-years.

Secondary Outcomes (13)

• Distant Disease-Free Survival (DDFS)

  From date of beginning of hormonotherapy to the date of first event of distant recurrence, death from any cause or secondary non-breast cancer up to 10 years

• Invasive disease free survival (iDFS)

  From date of beginning of hormonotherapy to onset of invasive event, second cancer, or death, up to 10 years.

• Invasive breast cancer-free survival (iBCFS)

  From date of beginning of hormonotherapy to onset of invasive event or death, up to 10 years.

• Breast cancer-specific survival (BCSS)

  From date of beginning of hormonotherapy to death from breast cancer, up to 10 years.

• Overall survival (OS)

  From date of beginning of hormonotherapy to death from any cause, up to 10 years.

Study Arms (1)

Aromatase inhibitor

EXPERIMENTAL

Patient will receive standard endocrine therapy (single agent aromatase inhibitors) for a maximum of 2 years.

Drug: Anti-aromatase inhibitor

Interventions

Anti-aromatase inhibitor DRUG

Treatment will be either: * Letrozole, given per os, 2.5 mg daily * Anastrozole, given per os, 1 mg daily * Exemestane, given per os, 25 mg daily

Aromatase inhibitor

Eligibility Criteria

• Age: 51 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women: Postmenopausal status is defined by any of the following:
• Prior bilateral oophorectomy
• Age ≥60 years
• Age \>50 and \<60 years and amenorrheic for at least 12 months, and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Women with histologically proven invasive unilateral breast cancer Note: In case of a multifocal invasive tumor, all lesions (maximum 3 infiltrating lesions allowed) must be of identical phenotype and low biological risk
• Primary tumor completely resected and adequate axillary surgery performed, according to current standards
• IHC expression of the estrogen receptor and/or progesterone receptor ≥50%
• HER2 negative according to ASCO criteria in immunohistochemistry and/or genomic analysis (HER2 negativity is defined as IHC 0-1+, or \[IHC 2+ and FISH or CISH nonamplified\])
• No indication of adjuvant chemotherapy
• pT1 (tumor ≤20 mm), pN0, Grade 1 or Grade 2 OR pT2 (tumor ≤30 mm) and pN0, Grade 1 or Grade 2
• Note 1: patient with Grade 2 pT2pN0 tumor must be aged under 70 years of age and should receive a genomic test as part of standard care (RIHN reimbursement)
• Patient considered has having a luminal A ultralow risk of metastatic recurrence (i.e.less than 5% risk of metastatic relapse at 10 years) according to MammaPrint® and Blueprint® tests.
• Note 1: To be eligible, MammaPrint index score should be \> +0.355
• Patients eligible to receive or have recently started (with a maximum of 4 months of adjuvant hormone therapy prior to enrollment) an adjuvant hormone therapy (letrozole, anastrozole, or exemestane)

You may not qualify if:

• Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment
• Any local or regional recurrence or metastatic disease
• Non-invasive carcinoma
• Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer
• Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin
• Women with high-risk breast cancer predisposing deleterious germline mutations
• Contra-indications to the administration of anti-aromatase inhibitors
• Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment
• Patients unwilling or unable to comply with trial obligations for geographic, social, physical or psychological reasons, or who are unable to understand the purpose and procedures of the trial
• Persons deprived of their liberty or under protective custody or guardianship

Sponsors & Collaborators

• UNICANCER: lead
• Agendia: collaborator

Study Sites (2)

Centre Hospitalier Universitaire de Limoges

Limoges, 87042, France

RECRUITING

Institute Gustave Roussy

Villejuif, 94805, France

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Elise DELUCHE, MD

  CHU Limoges

  STUDY CHAIR

• Fabrice André, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Central Study Contacts

Clara GUYONNEAU, PharmD

CONTACT

0685167111; c-guyonneau@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, national, multicenter, single-arm, interventional, non-threshold crossing phase II study evaluating a therapeutic de-escalation that limits adjuvant hormone therapy to 2 years of aromatase inhibitor

Study Record Dates

• First Submitted: March 16, 2022
• First Posted: March 28, 2022
• Study Start: October 12, 2022
• Primary Completion (Estimated): November 12, 2030
• Study Completion (Estimated): November 1, 2035
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)