Prediction of Everolimus-induced Interstitial Lung Disease

Breast Neoplasms Clinical Trial

— PREVENT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01978171
• Other study ID #: UMCNONCO201302
• Status: Completed
• First received: October 31, 2013
• Last updated: April 11, 2018
• Start date: May 2014
• Est. completion date: January 15, 2018

Study information

• Verified date: September 2017
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 15, 2018
• Est. primary completion date: January 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Lung Diseases
• Lung Diseases, Interstitial

Locations

Country	Name	City	State
Netherlands	Antonius Ziekenhuis	Nieuwegein
Netherlands	Radboud university medical center	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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