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

NCT ID: NCT02444390

Last Updated: 2022-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-19
• Study Completion Date: 2022-07-01

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

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Exemestane+everolimus

Exemestane+everolimus are administered as per their approved indication

Group Type: OTHER

Biopsy

Intervention Type: PROCEDURE

biopsy of a metastasis

Interventions

Biopsy

biopsy of a metastasis

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Fondation ARC

OTHER

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Bachelot, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Léon Bérard, Lyon, France

Locations

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

Saint-Priest-en-Jarez, , France

Centre Paul Strauss

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Institut de Cancerologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 38182687 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

UC-0105/1403

Identifier Type: -

Identifier Source: org_study_id