Prediction of Everolimus-induced Interstitial Lung Disease

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Primary Outcome Measures

Name	Time	Method
predictive factors of everolimus-induced ILD	six months	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

Secondary Outcome Measures

Name	Time	Method
temporal relation pneumoproteins and ILD	six months	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
pathophysiology of everolimus-induced ILD	six months	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
relation ILD and exposure and outcome	six months	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

Locations (2): Antonius Ziekenhuis
🇳🇱
Nieuwegein, Netherlands
Radboud university medical center
🇳🇱
Nijmegen, Netherlands

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