Breast Neoplasms
Conditions
Keywords
breast neoplasms, everolimus, interstitial lung disease, pneumonitis
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.
Interventions
None listed
Sponsors
Radboud University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Netherlands
Outcome results
None listed