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

NCT02444390 | Completed

• 1 other identifier: UC-0105/1403
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 12

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.

Conditions

Metastatic Breast Cancer

Keywords

Failed non steroidal aromatases inhibitors; Eligible for everolimus+exemestane

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Exemestane+everolimus

OTHER

Exemestane+everolimus are administered as per their approved indication

Procedure: Biopsy

Interventions

Biopsy PROCEDURE

biopsy of a metastasis

Exemestane+everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Eligible for everolimus+exemestane treatment as required by the marketing authorisation conditions
• 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
• Postmenopausal women
• Asymptomatic if visceral disease
• 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
• Treatment with everolimus and exemestane not yet started
• Patients with metastases that can be biopsied, except bone metastases
• Measurable or evaluable disease
• Age ≥18 years
• WHO Performance Status 0/1
• Provision of signed and dated, written informed consent prior to any protocol specific procedure, including biopsy
• Patient with social insurance coverage

You may not qualify if:

• Contraindications for everolimus+exemestane treatment
• Previous treatment with an anti-mTOR therapy
• More than 1 previous line of chemotherapy in metastatic setting
• Life expectancy \<3 months
• 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)
• 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
• Abnormal coagulation or any other medical situation contraindicating biopsy
• Bone metastases when this is the only site of biopsiable disease

Sponsors & Collaborators

• UNICANCER: lead
• Novartis: collaborator
• Fondation ARC: collaborator

Study Sites (12)

Institut de Cancérologie de l'Ouest/Paul Papin

Angers, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut de Cancérologie de l'Ouest/Rene Gauducheau

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Clinique Armoricaine de Radiologie

Saint-Brieuc, France

Location

INSTITUT DE CANCEROLOGIE Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut de Cancerologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Vanacker H, Treilleux I, Schiffler C, Bieche I, Campone M, Patsouris A, Arnedos M, Cottu PH, Jacquin JP, Dalenc F, Pinton A, Servant N, Attignon V, Rouleau E, Morel A, Legrand F, Jimenez M, Andre F, Bachelot T. p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane. Br J Cancer. 2024 Mar;130(4):613-619. doi: 10.1038/s41416-023-02549-8. Epub 2024 Jan 5.

  PMID: 38182687 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Thomas Bachelot, MD

  Centre Léon Bérard, Lyon, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 14, 2015
• Study Start: May 19, 2015
• Primary Completion: October 1, 2018
• Study Completion: July 1, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Locations

FR (12)