Clinical trial NCT01978171: Prediction of Everolimus-induced Interstitial Lung Disease
Official title: Prediction of Everolimus-induced Interstitial Lung Disease in Breast Cancer Patients; Maximizing Efficacy by Reducing Toxicity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Neoplasms
Keywords: breast neoplasms
everolimus
interstitial lung disease
pneumonitis
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2013-11-07
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

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.

Eligibility criteria: 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 outcomes:
measure: predictive factors of everolimus-induced ILD
timeFrame: six months
Secondary outcomes:
measure: temporal relation pneumoproteins and ILD
timeFrame: six months
measure: pathophysiology of everolimus-induced ILD
timeFrame: six months
measure: relation ILD and exposure and outcome
timeFrame: six months
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
Study officials:
affiliation: Radboud university medical center, department of medical oncology
name: Carla van Herpen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud university medical center, department of Pharmacy
name: Nielka van Erp, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Willemsen AECAB, Tol J, van Erp NP, Jonker MA, de Boer M, Meek B, de Jong PC, van Moorsel C, Gerritsen WR, Grutters JC, van Herpen CML. Prospective Study of Drug-induced Interstitial Lung Disease in Advanced Breast Cancer Patients Receiving Everolimus Plus Exemestane. Target Oncol. 2019 Aug;14(4):441-451. doi: 10.1007/s11523-019-00656-2.