Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients

NCT02511639 | Completed Phase 3

• 2 other identifiers: CRAD001JIT36T2013-004153-24
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 16

Brief Summary

The purpose of this study is to compare maintenance Aromatase Inhibitors (AIs) + everolimus with Aromatase Inhibitors alone after 1st line chemotherapy in patients with HR+ metastatic breast cancer.

Conditions

Breast Cancer Metastatic

Keywords

Hormone receptor positive; HER2 negative

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  PFS is defined as the time from randomization to the first documentation of objective disease progression or death from any cause

  Up to 2 years after randomisation

Secondary Outcomes (3)

• Overall survival

  Up to 2 years after randomisation

• Response rate

  Every 12 weeks during treatment, up to 2 years after randomisation

• Safety profile

  Baseline and every 4 weeks during treatment, up to 2 years after randomisation

Study Arms (2)

Arm A: Everolimus & Aromatase inhibitors

EXPERIMENTAL

Everolimus 10 mg po daily + Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)

Drug: Everolimus; Drug: Aromatase Inhibitors

Arm B: Aromatase inhibitors

ACTIVE COMPARATOR

Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)

Drug: Aromatase Inhibitors

Interventions

Everolimus DRUG

Everolimus is formulated as tablets of 10 mg strength for oral administration.

Arm A: Everolimus & Aromatase inhibitors

Aromatase Inhibitors DRUG

Anastrozole is formulated as tablets of 1 mg strength for oral administration. Letrozole is formulated as tablets of 2.5 mg strength for oral administration. Exemestane is formulated as tablets of 25 mg strength for oral administration.

Also known as: Exemestane, Letrozole, Anastrozole

Arm A: Everolimus & Aromatase inhibitors; Arm B: Aromatase inhibitors

Eligibility Criteria

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

You may qualify if:

• \>18 years old women with metastatic breast cancer
• Histological confirmation of hormone-receptor positive (defined as at least 10% of estrogen receptor (ER) and/or progesterone receptor (PgR) positivity) and human epidermal growth factor receptor 2 (HER2) negative (score 0-1+ in immunohistochemistry or FISH negativity) breast cancer
• Postmenopausal status
• One line of chemotherapy for metastatic disease; patients must have received a minimum of 6 cycles of chemotherapy in order to be eligible, and must have obtained disease control (CR or PR od SD)
• Eastern Cooperative Oncology Group (ECOG) Performance status \< 2
• Adequate bone marrow and coagulation function
• Adequate liver function
• Adequate renal function
• Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × upper limit of normal (ULN). In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved
• Fasting glucose \< 1.5 × ULN
• Written informed consent obtained before any screening procedure and according to local guidelines.

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (immunohistochemistry 3+ staining or in situ hybridization positive)
• Previous treatment with mammalian target of rapamycin (mTOR) inhibitors
• Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin)
• More than one chemotherapy line for metastatic disease
• Treatment with angiogenetic compounds as maintenance therapy (eg. bevacizumab)
• Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment
• Symptomatic central nervous system metastases
• Patients with a known history of HIV positivity
• Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the international normalized ratio (INR) is ≤ 2.0)
• Any severe and / or uncontrolled medical conditions such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 × ULN
• Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusion capacity of lung for carbon monoxide (DLco) and O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• University of Padova: collaborator

Study Sites (16)

Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

Ancona, AN, 60020, Italy

Location

Ospedale Papa Giovanni XXIII

Bergamo, Bg, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

Location

ASL Brindisi "Antonio Perrini"

Brindisi, BR, 72100, Italy

Location

Azienda Spedali Civili di Brescia

Brescia, BS, 25123, Italy

Location

A.S.O. S.Croce e Carle di Cuneo

Cuneo, CN, 12100, Italy

Location

Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"

Catania, CT, 95123, Italy

Location

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, FE, 44124, Italy

Location

Ospedale Misericordia di Grosseto

Grosseto, GR, 58100, Italy

Location

Istituto Nazionale dei Tumori IRCCS

Milan, MI, 20133, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, PR, 43126, Italy

Location

IRCCS - Azienda Ospedaliera S.M. Nuova

Reggio Emilia, RE, 42123, Italy

Location

Ospedale Civile Santa Chiara

Trento, TN, Italy

Location

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, UD, 33100, Italy

Location

Ospedale Sacro Cuore - Don Calabria

Negrar, VR, 37042, Italy

Location

Ospedale dell'Angelo

Mestre, 30174, Italy

Location

MeSH Terms

Interventions

Everolimus; Aromatase Inhibitors; exemestane; Letrozole; Anastrozole

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pierfranco Conte, MD, PhD

  Medical Oncology 2, Istituto Oncologico Veneto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 30, 2015
• Study Start: July 30, 2014
• Primary Completion: February 28, 2020
• Study Completion: July 31, 2020
• Last Updated: December 3, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (16)