Trial record 1 of 2482 for:    hormone therapy AND (woman OR women OR female)
Previous Study | Return to List | Next Study

Safety Study of Adding Everolimus to Adjuvant Hormone Therapy in Women With Poor Prognosis, ER+ and HER2- Primary Breast Cancer, Free of Disease After Receiving 3 Years of Adjuvant Hormone Therapy

This study is currently recruiting participants.
Verified December 2013 by UNICANCER
Sponsor:
Collaborator:
Netherlands: Ministry of Health, Welfare and Sports
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01805271
First received: December 6, 2012
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.

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.

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.


Condition Intervention Phase
ER-positive HER2-negative Breast Cancer
Drug: Everolimus
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double Blind, Multicentric Phase III Trial Evaluating the Safety and Benefit of Adding Everolimus to Adjuvant Hormone Therapy in Women With Poor Prognosis, ER+ and HER2- Primary Breast Cancer Who Remain Free of Disease After Receiving 3 Years of Adjuvant Hormone Therapy

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • To evaluate the benefit from adding everolimus to standard endocrine treatments after two years of treatment on the disease-free survival (DFS) after randomization. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of impact of everolimus on the overall survival (OS), the Event Free Survival (EFS) and Distant Metastasis Free Survival (DMFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assessment of impact of everolimus on DFS and OS in ER+,PR+ and ER+/PR- subgroups [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Impact of everolimus on the incidence of secondary cancers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assessment of the safety profiles for everolimus and hormone therapy combination. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Biology: Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • quality of life sub-studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1984
Study Start Date: March 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
2 tablets/day (i.e.10mg/day )
Drug: Everolimus
(10mg/day, i.e. 2 tablets/day)
Other Name: Afinitor
Placebo Comparator: Placebo
2 tablets/day
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women ≥ 18 years of age,
  2. Histologically proven invasive unilateral or bilateral breast cancer (regardless of the type),
  3. Any T, M0
  4. At least 4 positive lymph nodes if initial surgery, or at least 1 positive lymph node after neo-adjuvant chemotherapy or hormone therapy
  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 negative]
  6. Initial tumor completely resected (surgery could have been done before or after neoadjuvant chemotherapy/hormone therapy)
  7. Having received at least 2 years and 10 months but not more than 3 years and 6 months of adjuvant hormone therapy. Hormone therapy could be either tamoxifen, 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: ASAT and ALAT ≤ 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:

  1. Any local, regional or metastatic evolution.
  2. Any clinically or radiologically suspect and non-explored damage to the contra lateral breast.
  3. Previous cancer (excepted cutaneous baso-cellular epithelioma or uterine peripheral epithelioma) in the preceding 5 years, including invasive controlateral breast cancer.
  4. Patients already included in another ongoing therapeutic trial involving an experimental drug for which follow-up is required.
  5. Pregnant or breast-feeding patients. Adequate birth control measures should be taken during study treatment phase.
  6. Patients with severely impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)
  7. Positive serology for HIV infection or hepatitis C.
  8. Chronic carrier of HBV (positive Antigen HbS in the blood)
  9. Patients with chronic infection
  10. Uncontrolled diabetes defined as glycated haemoglobinemia > 7%
  11. Uncontrolled hypercholesterolemia (cholesterol >400 mg/dl under adequate therapy).
  12. Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients.
  13. Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study.
  14. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01805271

Contacts
Contact: Jerome LEMONNIER, PhD +33 1 7193 6702 j-lemonnier@unicancer.fr

Locations
France
Centre Leon Berard Recruiting
Lyon, France
Principal Investigator: Thomas Bachelot         
Gustave Roussy Recruiting
Villejuif, France
Principal Investigator: Fabrice Andre         
Sponsors and Collaborators
UNICANCER
Netherlands: Ministry of Health, Welfare and Sports
Investigators
Principal Investigator: Thomas Bachelot, MD, PhD Centre Leon Berard, Lyon, France
Principal Investigator: Fabrice Andre, MD, PhD Institut Gustave Roussy, Villejuif, France
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01805271     History of Changes
Other Study ID Numbers: UNIRAD, 2012-003187-44, UC-0140/1208
Study First Received: December 6, 2012
Last Updated: December 2, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Sirolimus
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014