We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05297617
Recruitment Status : Recruiting
First Posted : March 28, 2022
Last Update Posted : December 21, 2022
Sponsor:
Collaborator:
Agendia
Information provided by (Responsible Party):
UNICANCER

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Anti-aromatase inhibitor Phase 2

Detailed Description:
Adjuvant ET is the cornerstone treatment of localized hormone-receptor positive breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio may therefore become very questionable given the frequent and impactful side effects of ET. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather 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. The purpose of this study is to demonstrate that adjuvant hormone therapy limited to 2 years of antiaromatase in postmenopausal women with a good prognosis can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life. The 5-year DMFS was excellent in patients with low risk Luminal A tumors who received endocrine therapy.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 696 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-arm Study to De-escalate Adjuvant Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk of Metastasis
Actual Study Start Date : October 12, 2022
Estimated Primary Completion Date : November 2029
Estimated Study Completion Date : November 2034

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Aromatase inhibitor
Patient will receive standard endocrine therapy (single agent aromatase inhibitors) for a maximum of 2 years.
Drug: Anti-aromatase inhibitor

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




Primary Outcome Measures :
  1. Distant metastasis-free survival (DMFS) [ Time Frame: From inclusion to onset of metastases, up to 5-years. ]
    Distant metastasis-free survival is defined as the time from date of inclusion to date of first event of distant recurrence, death, or second primary non-breast invasive cancer.


Secondary Outcome Measures :
  1. Invasive disease free survival (iDFS) [ Time Frame: From inclusion to onset of invasive event, second cancer, or death, up to 10 years. ]
    Invasive disease free survival is defined as duration of time from date of registration until first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast cancer recurrence), invasive contralateral breast cancer, second primary non breast invasive cancer (excluding non-melanoma skin cancer), or death from any cause.

  2. Invasive breast cancer-free survival (iBCFS) [ Time Frame: From inclusion to onset of invasive event or death, up to 10 years. ]
    Invasive disease free survival is defined as the delay between date of inclusion and first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast cancer recurrence), invasive contralateral breast cancer, or death from any cause.

  3. Breast cancer-specific survival (BCSS) [ Time Frame: From inclusion to death from breast cancer, up to 10 years. ]
    Breast cancer-specific survival is defined as the time from inclusion to death from breast cancer.

  4. Overall survival (OS) [ Time Frame: From inclusion to death from any cause, up to 10 years. ]
    The overall survival is the length of time from inclusion to death from any cause.

  5. Quality of life (QoL) questionnaire - Core 30 (QLQ-C30) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]
    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

  6. Quality of life (QoL) questionnaire - EORTC QLQ-BR23/QLQ-BR45 [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]

    This EORTC breast cancer specific questionnaire is intended to supplement the QLQ-C30.

    The QLQ-BR23 contains 23 items incorporating five multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning. In addition, single items assess sexual enjoyment, hair loss and future perspective. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. For all items but sexual functioning and sexual enjoyment, higher scores indicate more severe symptoms. The QLQ-BR-23 was updated and 22 new questions were added to provide a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients'QoL


  7. Quality of life (QoL) questionnaire - Cancer related fatigue (QLQ-FA12) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]

    This EORTC cancer related fatigue questionnaire is intended to supplement the QLQ-C30.

    The QLQ-FA12 contains 12 items organized in three subscales: physical fatigue (5 items), emotional fatigue (3 items), and cognitive fatigue (2 items). The remaining two items serve as global indicators for interference of fatigue with daily activities and social sequelae of fatigue.

    All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale with higher scores indicating greater degree of fatigue.


  8. Hospital anxiety and depression scale (HADS) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]
    The HADS is a 14 items questionnaire: 7 items related to anxiety and 7 items related to depression scored on a scale. Scores for items in each subscale of the HADS are summed to produce an anxiety score (HADS-A) or a depression score (HADS-D), or can be added to produce a total score corresponding to emotional distress (HADS-T). Each item is rated on a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), for a total score ranging from 0-21 for each subscale. The entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.

  9. Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]
    The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales: cognitive impairments perceived by the patient (20 items), comments from others (4 items), cognitive abilities perceived by the patient (9 items), and impact on quality of life (4 items). The Perceived Cognitive Impairments and the Comments from Others subscales are rated on 5-point Likerttype scale (from 0 = "Never" to 4 = "Several times a day"). An intensity 5-point Likert-type scale (from 0 "Not at all" to 4 "Very much") is used to rate perceived cognitive abilities and the impact on quality of life. For all subscales, a higher score represents better cognitive functioning or quality of life.

  10. Impact of Cancer (including fear of recidivism) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]
    The Impact of Cancer Version 2 (IOCv2) is a 47-item questionnaire. The first 37 items are intended to measure 4 positive (Altruism/Empathy, Health Awareness, Meaning of Cancer, and Positive SelfEvaluation) and 4 negative (Appearance Concerns, Body Change Concerns, Life Interferences, and Worry) subscales, which total to two summary scores (Positive and Negative Impact). The 10 additional items constitute conditional dimensions applicable to subsets of survivors assessing employment concerns, relationship concerns for individuals with a partner, and relationship concerns for those without a partner. All items are scored on a five-point scale (1 = "strongly disagree", 2 = disagree, 3 = neutral, 4 = agree, and 5 = "strongly agree"). Higher scores on the positive impact indicate greater positive impacts, while higher scores on the negative impact indicate greater negative impacts.

  11. Geriatric Core Dataset (G-CODE) [ Time Frame: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years ]

    The G-CODE was developed by the DIalog for personALization of management in geriatric OncoloGy (DIALOG) intergroup to assess the general health status of the older patient.

    The G-Code contains 10 tools incorporating seven scales to assess social environment, functional status, mobility, nutritional status, cognitive status, depressive mood, and comorbidities. The total scale range 0-62. High score indicate better condition.


  12. Evaluate the safety of the treatment in the study population [ Time Frame: Throughout study completion, up to 10 years. ]
    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   51 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  3. 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
  4. M0: Not clinically nor radiologically detectable metastases at time of inclusion
  5. Primary tumor completely resected and adequate axillary surgery performed, according to current standards
  6. IHC expression of the estrogen receptor and/or progesterone receptor ≥50%
  7. 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])
  8. No indication of adjuvant chemotherapy
  9. 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: MammaPrint test is indicated for patients with pT1c-2, pN0/pN1mic and grade 2, with no indication of chemotherapy.

    Note 2: Up to 80 patients aged ≥65 years and pT1 (tumor ≤20 mm) and pN0 and grade 1 and Ki67 ≤10% will be recruited

    Note 3: To be eligible, MammaPrint index score should be > +0.355

  10. 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)
  11. Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures
  12. Patients must be affiliated to a Social Security System (or equivalent)
  13. Patient must have signed a written informed consent form 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 writing the patient's consent.

Exclusion Criteria:

  1. Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment
  2. Any local or regional recurrence or metastatic disease
  3. Non-invasive carcinoma
  4. Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer
  5. Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin
  6. Women with high-risk breast cancer predisposing deleterious germline mutations
  7. Contra-indications to the administration of anti-aromatase inhibitors
  8. Patients enrolled in another therapeutic study within 30 days prior to inclusion
  9. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment
  10. 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
  11. Persons deprived of their liberty or under protective custody or guardianship

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05297617


Contacts
Layout table for location contacts
Contact: Clara GUYONNEAU, PharmD 0685167111 c-guyonneau@unicancer.fr

Locations
Layout table for location information
France
Centre Hospitalier Universitaire de Limoges Recruiting
Limoges, France, 87042
Contact: Elise DELUCHE, MD         
Contact       elise.deluche@chu-limoges.fr   
Principal Investigator: Elise DELUCHE, MD         
Institute Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Fabrice ANDRE, Pr/MD         
Contact       FABRICE.ANDRE@gustaveroussy.fr   
Principal Investigator: Barbara PISTILLI, Dr         
Sponsors and Collaborators
UNICANCER
Agendia
Investigators
Layout table for investigator information
Study Chair: Elise DELUCHE, MD CHU Limoges
Study Chair: Fabrice André, MD Gustave Roussy, Cancer Campus, Grand Paris
Layout table for additonal information
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT05297617    
Other Study ID Numbers: UC-BCG-2103
2021-002889-41 ( EudraCT Number )
First Posted: March 28, 2022    Key Record Dates
Last Update Posted: December 21, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs