Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor

Metastatic Breast Cancer Clinical Trial

— SAFIR-TOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02444390
• Other study ID #: UC-0105/1403
• Status: Completed
• Phase: N/A
• Start date: May 19, 2015
• Est. completion date: July 1, 2022

Study information

• Verified date: September 2022
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: July 1, 2022
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 10?/L
• Platelets <100 x 10?/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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Procedure:
• Biopsy
biopsy of a metastasis

Locations

Country	Name	City	State
France	Institut de Cancérologie de l'Ouest/Paul Papin	Angers
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Léon Bérard	Lyon
France	Institut de Cancérologie de l'Ouest/Rene Gauducheau	Nantes
France	Centre Antoine Lacassagne	Nice
France	Institut Curie	Paris
France	Clinique Armoricaine de Radiologie	Saint-Brieuc
France	INSTITUT DE CANCEROLOGIE Lucien Neuwirth	St PRIEST EN JAREZ
France	Centre Paul Strauss	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Institut de Cancerologie de Lorraine Alexis Vautrin	Vandoeuvre-les-nancy
France	Gustave Roussy	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
UNICANCER	Fondation ARC, Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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