breast cancer mamma carcinoma
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Eligible for inclusion are women who are planned to start treatment with everolimus in combination with exemestane as decided by their treating physician, if the patient is willing and able to sign the Informed Consent Form. The following general criteria can be used to determine whether a patient is suitable for treatment with everolimus and exemestane. Renal insufficiency and pulmonary disease are not considered an exclusion criterion. - 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. Postmenopausal status is defined either by: o Age * 55 years and one year or more of amenorrhea o Age
Exclusion criteria
Exclusion criteria: - Patients with a HER2-overexpressing tumor by local laboratory testing (IHC 3+ staining or amplification defined as locus/centromere ratio > 2.2 on fluorescent situ hybridization (FISH) or cytochromic in situ hybridization (CISH)) - 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 |
|---|---|
| Find the correlation between: - baseline patient characteristics (smoking, preexistent lung disease) - pneumoproteins; KL-6, surfactant protein A, surfactant protein D, CC16, CCL18, YKL-40, LDH and CA 15.3 (absolute number and difference from baseline) - everolimus exposure (AUC on day 14 and mini-AUC at moment of toxicity) - pulmonary function tests: spirometry including FVC and DLCO adjusted for hemoglobin (absolute number and difference from baseline) - four distinct radiological patterns of 1.0mm CT slices of the lungs (as described in paragraph 6.2.7, page 30) - the development and grade of everolimus-induced skin toxicity and oral mucositis and the development and grade of everolimus-induced ILD, using univariate and multivariate analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| - 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 - Investigate which immunological changes (cytokines, T-cells, dendritic cells) are observed in peripheral blood, skin biopsies and bronchoalveolar lavage of patients with everolimus-induced toxicity - Assess the duration and severity of ILD when patients are treated according to a standardized diagnostic and treatment strategy - Define the correlation between everolimus induced ILD on the one hand and everolimus exposure (as per AUC0-24h) on day 14) and outcome (as per PFS) on the other hand - Determine the type and frequency of lung parenchymal changes and its discriminative power from other (not drug-related) lung changes - Describe the quantity and quality of differences in judgment of HRCT images between a local and a central radiologist - Correlate everolimus exposure in saliva with serum AUC - Correlate everolimus exposure in saliva with incidence of oral mucositis | — |
Countries
Netherlands
Outcome results
None listed