Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor (SAFIR-TOR)

Identification of the Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor of HR+ Metastatic Breast Cancer in Post-menopausal Women

This is a prospective biomarker study to show that p4EBP1 staining predicts clinical benefit from treatment with everolimus in patients who are eligible for everolimus+exemestane treatment. This trial is not aimed at evaluating a drug activity. Everolimus and exemestane are prescribed within their approved indication as per usual practice and are not part of this trial.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Procedure: Biopsy

Detailed Description

Estrogen hormone receptor-positive metastatic breast cancer who failed to non steroidal aromatases inhibitors in patients who are eligible for everolimus+exemestane treatment

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Institut de Cancérologie de l'Ouest/Paul Papin
  • Clermont-Ferrand, France
    • Centre Jean Perrin
  • Lyon, France
    • Centre Leon Berard
  • Nantes, France
    • Institut de Cancérologie de l'Ouest/Rene Gauducheau
  • Nice, France
    • Centre Antoine Lacassagne
  • Paris, France
    • Institut Curie
  • Saint-Brieuc, France
    • Clinique Armoricaine de Radiologie
  • St PRIEST EN JAREZ, France
    • Institut de Cancérologie Lucien Neuwirth
  • Strasbourg, France
    • Centre Paul Strauss
  • Toulouse, France
    • Institut Claudius Regaud
  • Vandoeuvre-les-nancy, France
    • Institut de Cancérologie de Lorraine Alexis Vautrin
  • Villejuif, France
    • Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Eligible for everolimus+exemestane treatment as required by the marketing authorisation conditions

1. Women (or men) with histologically-proven Estrogen Receptor-positive (ER+) and/or Progesterone Receptor-positive (PR+) / Human Epidermal growth factor Receptor 2-negative (HER2-) metastatic breast adenocarcinoma or locally advanced disease who cannot be treated with surgery and/or radiation therapy
2. Postmenopausal women
3. Asymptomatic if visceral disease

4. Second line hormonotherapy or more for metastatic or locally advanced disease after recurrence or progression following a non-steroidal aromatase inhibitor (in adjuvant or metastatic setting)

   - Eligible for the biopsy

5. Progressive disease under endocrine therapy at the time of inclusion
6. Treatment with everolimus and exemestane not yet started
7. Patients with metastases that can be biopsied, except bone metastases
8. Measurable or evaluable disease
9. Age ≥18 years
10. WHO Performance Status 0/1
11. Provision of signed and dated, written informed consent prior to any protocol specific procedure, including biopsy
12. Patient with social insurance coverage

Exclusion Criteria:

1. Contraindications for everolimus+exemestane treatment
2. Previous treatment with an anti-mTOR therapy
3. More than 1 previous line of chemotherapy in metastatic setting
4. Life expectancy <3 months
5. Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug)

6. Haematopoietic function or organ impairment as shown by the following criteria:

   • Polynuclear neutrophils <1.5 x 10⁹/L
   • Platelets <100 x 10⁹/L
   • Haemoglobin <90 g/L
   • Alanine aminotransferase (ALAT) / aspartate aminotransferase (ASAT) >2.5 x ULN in the absence of or >5 x upper limit of normal (ULN) in the presence of liver metastases
   • Bilirubin >1.5 x ULN
   • Creatinine clearance ≤50 mL/min (measured or calculated by Cockcroft and Gault formula)
   • Calcium and phosphate >ULN
7. Abnormal coagulation or any other medical situation contraindicating biopsy
8. Bone metastases when this is the only site of biopsiable disease
9. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
10. Individuals deprived of liberty or placed under the authority of a tutor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Exemestane+everolimus; Exemestane+everolimus are administered as per their approved indication	Procedure: Biopsy; biopsy of a metastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the predictive value of p4EBP1 for an mTOR inhibitor efficacy	The primary endpoint of the trial is the predictive value of p4EBP1 for an mTOR inhibitor efficacy, measured by the association between expression level of the biomarker (high vs low expression with a cutoff value set at the median percentages of marked cells) and clinical benefit after 6 months of everolimus+exemestane treatment.	from inclusion up to 6 months

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Novartis; Fondation ARC
• Investigators: Principal Investigator: Thomas Bachelot, MD, Centre Léon Bérard, Lyon, France

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2015
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 13, 2015
• First Posted (Estimate): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Failed non steroidal aromatases inhibitors; Eligible for everolimus+exemestane
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: UC-0105/1403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED