Ipilimumab-induced Lung Toxicity: Observational Study (Ipi-Lu-Tox)

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Other: Pulmonary Function

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 71

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Department of Pulmonology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients in whom a treatment with ipilimumab due to metastatic melanoma is indicated

Description

Inclusion Criteria:

• Established diagnosis of metastatic melanoma

Exclusion Criteria:

• Acute pulmonary infection at enrolment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pulmonary function; Patients in whom treatment with ipilimumab due to metastatic melanoma is indicated

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); Other Names: Spirometry and CO-diffusion capacity measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Daniel Franzen, MD, University Hospital Zurich, Divison of Pneumology

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: April 15, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (ESTIMATE): April 28, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): April 28, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2013-0191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Additional supporting file