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

Not Applicable

Completed

• Conditions: Metastatic Breast Cancer
• Interventions: Procedure: Biopsy

• Registration Number: NCT02444390
• Lead Sponsor: UNICANCER

Brief 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.

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 Timeline

• Study First Submitted: 2015-05-11
• Study First Submitted QC: 2015-05-13
• Study First Posted: 2015-05-14
• Study Start: 2015-05-19
• Primary Completion: 2018-10
• Study Completion: 2022-07-01
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-19
• Last Update Posted: 2022-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Exemestane+everolimus	Biopsy	Exemestane+everolimus are administered as per their approved indication

Primary Outcome Measures

Name	Time	Method
the predictive value of p4EBP1 for an mTOR inhibitor efficacy	from inclusion up to 6 months	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.

Trial Locations

Locations (12)

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Clinique Armoricaine de Radiologie; 🇫🇷 Saint-Brieuc, France

Institut de Cancerologie de Lorraine Alexis Vautrin; 🇫🇷 Vandoeuvre-les-nancy, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Gustave Roussy; 🇫🇷 Villejuif, France

Institut de Cancérologie de l'Ouest/Rene Gauducheau; 🇫🇷 Nantes, France

Institut Curie; 🇫🇷 Paris, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Institut de Cancérologie de l'Ouest/Paul Papin; 🇫🇷 Angers, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France

INSTITUT DE CANCEROLOGIE Lucien Neuwirth; 🇫🇷 St PRIEST EN JAREZ, France