prediction of everolimus-induced interstitial lung disease in breast cancer patients; maximizing efficacy by reducing toxicity

Phase 4

Completed

Conditions: breast cancer
mamma carcinoma
10006291

Registration Number: NL-OMON38563

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 100

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 < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
o Surgical menopause with bilateral oophorectomy
- 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 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

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Find the correlation between:<br /><br>- baseline patient characteristics (smoking, preexistent lung disease)<br /><br>- pneumoproteins; KL-6, surfactant protein A, surfactant protein D, CC16,<br /><br>CCL18, YKL-40, LDH and CA 15.3 (absolute number and difference from baseline)<br /><br>- everolimus exposure (AUC on day 14 and mini-AUC at moment of toxicity)<br /><br>- pulmonary function tests: spirometry including FVC and DLCO adjusted for<br /><br>hemoglobin (absolute number and difference from baseline)<br /><br>- four distinct radiological patterns of 1.0mm CT slices of the lungs (as<br /><br>described in paragraph 6.2.7, page 30)<br /><br>- the development and grade of everolimus-induced skin toxicity and oral<br /><br>mucositis<br /><br>and the development and grade of everolimus-induced ILD, using univariate and<br /><br>multivariate analysis.</p><br>

Secondary Outcome Measures