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Primary Non-metastatic Breast CancerPhase 3NCT01805271

Safety Study of Adding Everolimus to Adjuvant Hormone Therapy in Women With High Risk of Relapse, ER+ and HER2- Primary Breast Cancer, Free of Disease After Receiving at Least One Year of Adjuvant Hormone Therapy

A Phase 3 study testing Everolimus in people with Primary Non-metastatic Breast Cancer and Who Remain Disease-free, run by UNICANCER at 2 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

A significant number of patients relapse and eventually die, particularly if they were initially diagnosed with large nodes involvement and/or T3/4 diseases. When analyses focus on patients with ER+/Her2-negative breast cancer, with ≥4N+, 30% had relapsed at 5 years, emphasizing the need for new drugs in this setting… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,278 participants
Where
2 sitesFrance
Study dates
Mar 2013to Jun 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female ≥18 years of age,
  • Histologically proven invasive unilateral or bilateral breast cancer (regardless of the morphological subtype),
  • Any T, M0
  • Patient with high risk of relapse according to one of the conditions below:
  • at least 4 positive lymph nodes if the patient had primary surgery
  • or at least 1 positive lymph node if surgery was conducted after neo adjuvant chemotherapy or hormone therapy of at least 3 months duration
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  • or 1-3 positive lymph nodes (pN1a, b, c) at primary surgery AND EPClin score ≥3.32867 Note: Access to primary tumor for patients with 1-3 node positive is mandatory. Patient with EPClin score <3.32867 will not be randomized, but will be followed yearly during 10 years
  • ER+ and HER2 negative : Hormone receptor positive is defined as any staining on the primary tumor, HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and FISH or CISH non-amplified]
  • Primary tumor completely resected (deep margins and overlying skin involvement allowed if fully resected)
  • Patients who will begin an adjuvant hormone therapy or have received a maximum of 4 years of adjuvant hormone therapy. Hormone therapy could be either +/- LH-RH agonists, letrozole, anastrozole or exemestane.
  • No clinically or radiologically detectable metastases at time of inclusion.
  • WHO Performance status (ECOG) of 0 or 1.
  • Adequate hematological function (neutrophil count ≥2x10⁹/L; platelet count ≥ 100x10⁹/L)
  • Adequate hepatic function: AST and ALT ≤2.5 ULN, alkaline phosphatases ≤2.5 ULN, total bilirubin ≤2 ULN
  • Adequate renal function: serum creatinine ≤1.5 ULN
  • Signed written informed consent

Who cannot join

  • Any local, or regional recurrence or metastatic disease
  • Any clinical or radiological suspicion of malignant or pre-malignant disease in the contralateral breast
  • Patients with pN1mi as sole nodal involvement
  • Previous cancer (excepted basal cell carcinoma of the skin or in situ carcinoma of the cervix) in the preceding 5 years, including invasive contralateral breast cancer
  • Patient already included in another ongoing therapeutic trial involving an unlicensed drug for which follow-up is required
  • Patient who is pregnant or breast-feeding. Adequate birth control measures should be taken during the study treatment phase
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  • Patient with significantly impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)
  • Positive serology for HIV infection or hepatitis C
  • Chronic carrier of HBV (positive Antigen HbsAg positive in the blood)
  • Patient with chronic infection
  • Uncontrolled diabetes defined as glycated haemoglobin , HbA1c >7%
  • Uncontrolled hypercholesterolemia (cholesterol >300 mg/dl under adequate therapy)
  • Known hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients
  • Patient with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study (e.g. patient who regularly require systemic steroids to control co-morbid disease)
  • Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Centre Leon Berard

    Lyon

  • Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: Randomized, Double Blind, Multicentric Phase III Trial Evaluating the Safety and Benefit of Adding Everolimus to Adjuvant Hormone Therapy in Women With High Risk of Relapse, ER+ and HER2- Primary Breast Cancer Who Remain Free of Disease After Receiving at Least 1 Year of Adjuvant Hormone Therapy

A significant number of patients relapse and eventually die, particularly if they were initially diagnosed with large nodes involvement and/or T3/4 diseases. When analyses focus on patients with ER+/Her2-negative breast cancer, with ≥4N+, 30% had relapsed at 5 years, emphasizing the need for new drugs in this setting (PACS01 data, UNICANCER internal data).

Strong evidence suggests that cross-talk between the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and ER signaling is linked to hormone resistance in breast cancer patients.

Read more

In the present study, we plan to evaluate the benefit from adding everolimus to standard endocrine treatments after three years of treatment for patient ER+/HER2- at high risk of relapse due to high nodes involvement (≥4) and/or persistent node involvement after neo-adjuvant chemotherapy.

Genomic signatures have emerged during the last 10 years as a new and additive means to evaluate more precisely long term prognosis, and in some instances the amount of benefit from chemotherapy or endocrine therapy in the adjuvant setting. Therefore, the UNIRAD study can be proposed to patients with 1-3 positive lymph nodes at primary surgery and a high risk of relapse with the EndoPredict test.

This study is a unique opportunity to prove the efficacy of everolimus in adjuvant setting. The study could be practice changing in case of positive results and could allow improving outcome of breast cancer patients presenting high risk of metastatic relapse.

Being tested
Everolimus, Placebo
Keywords
ER-positive HER2-negative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Afinitor

    (5 or 10 mg/day, i.e. 1 or 2 tablets/day)

  • PlaceboDrug

    (5 or 10 mg/day, i.e. 1 or 2 tablets/day)

Study groups in NCT01805271
Study groupRoleWhat they receive
EverolimusExperimental1 or 2 tablets/day (i.e.5 or 10 mg/day )
Receives: Drug: Everolimus
PlaceboPlacebo comparator1 or 2 tablets/day
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the benefit from adding everolimus to standard endocrine treatments after two years of treatment on the disease-free survival (DFS)

    Measured: 2 years

Secondary outcomes (6)

  1. Assessment of impact of everolimus on the overall survival (OS), the Event Free Survival (EFS) and Distant Metastasis Free Survival (DMFS)

    Measured: 2 years

  2. Assessment of impact of everolimus on DFS and OS in ER+,PR+ and ER+/PR- subgroups

    Measured: 2 years

  3. Impact of everolimus on the incidence of secondary cancers

    Measured: 2 years

  4. Assessment of the safety profiles for everolimus and hormone therapy combination.

    Measured: 2 years

  5. Biology: Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP.

    Measured: 2 years

  6. quality of life sub-studies

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2013 (estimated)
  2. Study startMar 2013
  3. Primary completionJun 2020
  4. Study completionJun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01805271
Sponsor's protocol ID
UNIRAD
Other IDs
2012-003187-44, UC-0140/1208
Status last verified
Jul 2026
First submitted
6 Dec 2012
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Bidard FC, Gessain G, Bachelot T, Frechin L, Vincent-Salomon A, Drubay D, Lemonnier J, Walter T, Penault-Llorca F, Martin AL, Gaudin C, Bichat A, Sassi F, Berlemont S, Chavez-MacGregor M, Rugo HS, Badoual C, Pistilli B, Ribeiro J, Di Meglio A, Lacroix-Triki M, Vaz Luis I, Lerousseau M, Andre F. Identifying Patients With Low Relapse Rate Despite High-Risk Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: Development and Validation of a Clinicopathologic Assay. J Clin Oncol. 2025 Oct;43(28):3090-3101. doi: 10.1200/JCO-25-00742. Epub 2025 Aug 22.

    PubMed 40845255

  • Giacchetti S, Laas E, Bachelot T, Lemonnier J, Andre F, Cameron D, Bliss J, Chabaud S, Hardy-Bessard AC, Lacroix-Triki M, Canon JL, Debled M, Campone M, Cottu P, Dalenc F, Ballesta A, Penault-Llorca F, Asselain B, Dumas E, Reyal F, Gougis P, Levi F, Hamy AS. Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial. EBioMedicine. 2024 Jun;104:105141. doi: 10.1016/j.ebiom.2024.105141. Epub 2024 May 7.

    PubMed 38718683

  • Bachelot T, Cottu P, Chabaud S, Dalenc F, Allouache D, Delaloge S, Jacquin JP, Grenier J, Venat Bouvet L, Jegannathen A, Campone M, Del Piano F, Debled M, Hardy-Bessard AC, Giacchetti S, Mouret-Reynier MA, Barthelemy P, Kaluzinski L, Mailliez A, Legouffe E, Sephton M, Bliss J, Canon JL, Penault-Llorca F, Lemonnier J, Cameron D, Andre F. Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. J Clin Oncol. 2022 Nov 10;40(32):3699-3708. doi: 10.1200/JCO.21.02179. Epub 2022 May 23.

    PubMed 35605174

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Everolimus in people with Primary Non-metastatic Breast Cancer and Who Remain Disease-free, run by UNICANCER at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the benefit from adding everolimus to standard endocrine treatments after two years of treatment on the disease-free survival (DFS) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01805271, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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