Ipilimumab-induced Lung Toxicity: Observational Study

Metastatic Melanoma Clinical Trial

— Ipi-Lu-Tox  

Official title:

Ipilimumab-induced Lung Toxicity: A Prospective Observational Study on Pulmonary Function Changes in Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02755233
• Other study ID #: 2013-0191
• Status: Completed
• Phase: N/A
• First received: April 15, 2016
• Last updated: April 25, 2016
• Start date: January 2014
• Est. completion date: March 2016

Study information

• Verified date: April 2016
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Observational

Clinical Trial Summary

Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with MM before and during treatment with ipilimumab are performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined clinically meaningful, thus indicative for pulmonary toxicity.

Description:

The aim of this prospective observational study is to determine the prevalence of ipilimumab lung toxicity defined by a significant decline of the diffusing capacity of the lung for carbon monoxide (DLCO) and/or forced vital capacity (FVC) in patients with MM.

Patients aged over 18 years with an established diagnosis of MM who are treated and followed up at the Department of Dermatology are asked to participate in the study after the indication for treatment with ipilimumab is given by the interdisciplinary skin tumorboard conference. After written informed consent is obtained, patients undergo a baseline evaluation (V1) including a medical history, physical examination, laboratory analyses (hemoglobin, leucocytes count, C-reactive protein, and pulmonary function tests (PFTs) with spirometry and measurement of DLCO. Thereafter, the first dose of ipilimumab (3mg/kg) is given intravenously over a period of 90 minutes without premedication. The subsequent three doses of ipilimumab are administered three weekly with analogue dose. Subsequent study visits (V2, V3, V4) including PFTs are scheduled on the same day as ipilimumab is administered. Thus, study visits are thoroughly adapted to the clinical visits, which is given by the administration of ipilimumab (total of four injections each separated by three weeks). In case of new respiratory symptoms during the study period, additional PFTs and a high-resolution computed tomography (HR-CT) of the chest are performed. In case of early study termination during follow-up pulmonary function test values which are already obtained are used for the final analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Established diagnosis of metastatic melanoma

Exclusion Criteria:

• Acute pulmonary infection at enrolment

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Metastatic Melanoma

Intervention

Other:
• Pulmonary Function
Spirometry and DLCO were measured according to performance standards based on the statements from the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Values of DLCO were adjusted for the patient's current hemoglobin value, and the patients were asked to withhold cigarette smoking at least four hours before pulmonary function testing. Lung volumes and DLCO were measured with a commercial ZAN300 CO Diffusion system (nSpire Health GmbH, Oberthulba, Germany)

Locations

Country	Name	City	State
Switzerland	Department of Pulmonology	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative reduction of DLCO of more than 15% from the baseline value during follow-up	A relative reduction of =15% from baseline of DLCO was chosen as clinically meaningful, thus indicative of a possible interstitial lung disease as a consequence of ipilimumab induced pulmonary toxicity	9 weeks	No
Secondary	Relative reduction of FVC of more than 10% from the baseline value during	A relative reduction of FVC of =10% from baseline was chosen as clinically meaningful, thus indicative of a possible interstitial lung disease as a consequence of ipilimumab induced pulmonary toxicity	9 weeks	No