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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Jun 2013 → ongoing

Decision date (initial)

2024-08-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health PHRc 2012 · La ligue contre le Cancer · Myriad Genetics · Cancer Research-UK · Novartis

External identifiers

EU CT number

2024-516198-61-00

EudraCT number

2012-003187-44

ClinicalTrials.gov

NCT01805271

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the benefit on disease-free survival (DFS) from adding 2 years everolimus to standard endocrine treatments.

Secondary objectives 9

1. Efficacy : Assessment of impact of everolimus on the overall survival (OS), the Event Free Survival (EFS), Distant Metastasis Free Survival (DMFS) and Bone Metastatic Free survival (BMFS)
2. Efficacy : Assessment of impact of everolimus on DFS and OS in ER+,PR+ and ER+/PR- subgroups
3. Efficacy : Assessment of impact of everolimus on the incidence of secondary cancers
4. Toxicity : Assessment of the safety profile of everolimus in combination with hormone therapy.
5. Biological : Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP
6. Biological : Other translational analyses linking cancer biology with outcomes
7. Others : Quality of life sub-studies
8. Others : EFS and DMFS in low risk patients (according to the EPClin score)
9. Others : Sociologic study

Conditions and MedDRA coding

Patients with high risk of relapse, ER+ and HER2- primary non-metastatic breast cancer who remain disease-free

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Female ≥ 18 years of age
2. Histologically proven invasive unilateral or bilateral breast cancer (regardless of the morphological subtype)
3. Any T, M0
4. Patient with high risk of relapse
5. 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]
6. Primary tumor completely resected (deep margins and overlying skin involvement allowed if fully resected)
7. 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 tamoxifen +/- LH-RH agonists, letrozole, anastrozole or exemestane
8. No clinically or radiologically detectable metastases at time of inclusion.
9. WHO Performance status (ECOG) of 0 or 1.
10. Adequate hematological function (neutrophil count  2x109/l, platelet count  100x 109/l)
11. Adequate hepatic function: AST and ALT ≤ 2.5 ULN, alkaline phosphatases ≤ 2.5 ULN, total bilirubin ≤ 2 ULN.
12. Adequate renal function: serum creatinine ≤ 1.5 ULN
13. Signed written informed consent.

Exclusion criteria 15

1. Any local or regional recurrence or metastatic disease.
2. Any clinical or radiological suspicion of malignant or pre-malignant disease in the contralateral breast.
3. Patients with pN1mi as sole nodal involvement
4. 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.
5. Patient already included in another ongoing therapeutic trial involving an unlicensed drug for which follow-up is required.
6. Patient who is pregnant or breast-feeding. Adequate birth control measures should be taken during the study treatment phase.
7. Patient with significantly impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)
8. Positive serology for HIV infection or hepatitis C.
9. Chronic carrier of HBV (positive Antigen HbsAg positive in the blood)
10. Patient with chronic infection
11. Uncontrolled diabetes defined as glycated haemoglobin , HbA1c>7%
12. Uncontrolled hypercholesterolemia (cholesterol >300 mg/dl under adequate therapy).
13. Known hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients.
14. 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).
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival rate (DFS) after randomisation (disease is defined as local, regional or metastatic relapse, a new contralateral breast cancer, or death from any cause).

Secondary endpoints 13

1. Efficacy : Overall survival rate (OS) for the whole population
2. Efficacy : DFS and OS for ER+ and PR+ subgroup
3. Efficacy : DFS and OS for the ER+/PR – subgroup
4. Efficacy : EFS
5. Efficacy : DMFS
6. Efficacy : BMFS
7. Efficacy : Secondary cancer
8. Toxicity : CTC-AE scale version 4.0.
9. Biological : Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP
10. Biological : Other translational analyses linking cancer biology with outcomes
11. Other : Quality of life: QLQ C30
12. Other : EFS and DMFS in low risk patients (according to the EPClin score)
13. Other : Sociologic study

Investigational products

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

Test 1

Placebo 1

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

2 EU/EEA countries · 52 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 16 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