Prediction of Everolimus-induced Interstitial Lung Disease

Study Overview
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Brief Summary
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The investigators will determine which factors are predictive for the development and severity of everolimus-induced interstitial lung disease and will develop a prediction model based on these risk factors.

Detailed Description
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In this study the investigators will prospectively investigate pulmonary adverse events during treatment with everolimus. The investigators will distinguish the following everolimus-induced pulmonary adverse events: pulmonary infection, everolimus-induced airway disease and everolimus-induced interstitial lung disease (ILD). The investigators will investigate the predictive value of pneumoproteins, everolimus exposure, pulmonary function tests, four distinct radiological patterns, baseline patient characteristics and the development of skin toxicity or oral mucositis for the development and severity of everolimus-induced ILD.

Official Title
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Prediction of Everolimus-induced Interstitial Lung Disease in Breast Cancer Patients; Maximizing Efficacy by Reducing Toxicity

Conditions
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Breast Neoplasms

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer Postmenopausal women Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment Resistance to treatment with a non-steroidal aromatase inhibitor Serum platelets ≥ 100x10E9/l Everolimus dose adjustment is recommended for patients with hepatic impairment (Child-Pugh A/B/C) Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100) Exclusion Criteria: Patients with a HER2-overexpressing tumor Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin). Patients with a known history of HIV seropositivity or hepatitis B or C Uncontrolled diabetes mellitus 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) Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| breast cancer patients<br>Postmenopausal women with estrogen receptor (ER) positive advanced breast cancer whose disease is refractory to non steroidal aromatase inhibitors, and are eligible for treatment with exemestane and everolimus. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictive factors of everolimus-induced ILD | Find the correlation between: pneumoproteins everolimus exposure pulmonary function tests four distinct radiological patterns of 1.0mm CT slices of the lungs baseline patient characteristics the development and grade of everolimus-induced skin toxicity and oral mucositis and the development and grade of everolimus-induced ILD | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| temporal relation pneumoproteins and ILD | Analyze the temporal relationship between a decrease in pulmonary function or the occurrence of new radiological pulmonary abnormalities and an increase in the level of pneumoproteins | six months | 
| pathophysiology of everolimus-induced ILD | Investigate which immunological changes (cytokines, T-cells, dendritic cells) are observed in peripheral blood, skin biopsies and bronchoalveolar lavage fluid of patients with everolimus-induced toxicity | six months | 
| relation ILD and exposure and outcome | Define the correlation between everolimus-induced ILD on the one hand and everolimus exposure (as per AUC0-24h) on day 14) and outcome (time to progression, as determined by treating physician) on the other hand | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast neoplasms, everolimus, interstitial lung disease, pneumonitis