Clinical trial NCT02444390: Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Breast Cancer
Keywords: Failed non steroidal aromatases inhibitors
Eligible for everolimus+exemestane
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Novartis
name: Fondation ARC
First posted: 2015-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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

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

Primary outcomes:
measure: the predictive value of p4EBP1 for an mTOR inhibitor efficacy
timeFrame: from inclusion up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest/Paul Papin
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest/Rene Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Saint-Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: St PRIEST EN JAREZ
country: France
facility: INSTITUT DE CANCEROLOGIE Lucien Neuwirth
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre-les-nancy
country: France
facility: Institut de Cancerologie de Lorraine Alexis Vautrin
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
affiliation: Centre Léon Bérard, Lyon, France
name: Thomas Bachelot, MD
role: PRINCIPAL_INVESTIGATOR
References: