Study to Evaluate the Efficacy and Safety of Nintedanib (BIBF 1120) + Prednisone Taper in Patients With Radiation Pneumonitis

Lung Cancer Clinical Trial

Official title:

Phase II Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Nintedanib (BIBF 1120) + Prednisone Taper in Patients With Radiation Pneumonitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02496585
• Other study ID #: 14-167
• Status: Completed
• Phase: Phase 2
• Start date: July 8, 2015
• Est. completion date: April 12, 2024

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out what effects, good and/or bad, the drug nintedanib in combination with steroids, has on the lungs. Furthermore, such treatments' side effects will be studied together with quality of life. In addition, the investigators would like to determine whether they can find markers in the blood which predict worsening lung injury.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: April 12, 2024
• Est. primary completion date: April 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically/cytologically proven primary thoracic or breast malignancy, lymphoma or lung metastases (which are not required to be biopsy-proven) treated with definitive intent at MSK

• Prior treatment with thoracic radiotherapy completed >4 weeks and = 9 months prior to enrollment

• Radiographic evidence of radiation pneumonitis on a CT scan of the chest with or without contrast

• Newly diagnosed clinical grade 2 or higher radiation pneumonitis according to CTCAE version 4.0 criteria

• Age=18 years

• KPS > 70%

• Reduction of any acute toxicity from radiation treatment to grade 1

• Written informed consent signed prior to entry into the study

Exclusion Criteria:

• Current oral steroid use > 4 weeks prior to registration

• Ongoing treatment with radiotherapy to thorax, cytotoxic or biological therapies for this malignancy, except the following therapies which are permitted: Pembrolizumab, Nivolumab, Afatinib and all hormonal therapies.

• Mean esophageal radiation dose >45 Gy

• Diagnosis of diffuse radiation pneumonitis

• Untreated or symptomatic brain metastases or leptomeningeal disease

• Liver metastases

• Other active malignancies requiring oncologic treatment (Note: non-melanoma skin cancer, superficial bladder cancer etc. are eligible)

• Radiographic evidence of cavitary or necrotic tumor and local invasion of major blood vessels

• Active chronic Hepatitis C and/or B infection

• Gastrointestinal disorders that would interfere with drug absorption

• AST > 1.5 x ULN, ALT>1.5 x ULN and Bilirubin > 1.5 x ULN

• = Grade 2 proteinuria, creatinine >1.5x ULN or GFR <45 ml/min

• Other investigational therapy received within 8 weeks prior to screening visit

• Pregnant women or women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to enrollment1

• Sexually active males not committing to birth control during the course of the study (except if their partner is not of childbearing potential)

• Conditions that may affect the patient's ability to participate in this trial, e.g. known or suspected active alcohol or drug abuse

• Inherited predisposition to bleeding or thrombosis, INR >2, PT and PTT >1.5x ULN

• History of bleeding disorders or thrombotic events, e.g. hemorrhagic or thrombotic events within 12 months, clinically significant or tumor-related hemoptysis, active gastrointestinal bleeding or ulcers or major injuries or surgery

• ANC < 1.5 K/mcL, Platelets < 100 K/mcL, Hemoglobin < 9.0 g/dl

• Concomitant treatment with any of the following drugs: azathioprine, cyclophosphamide, cyclosporine, pirfenidone, full dose anticoagulation (vitamin K antagonists, dabigatran, heparin, etc.), fibrinolysis and high dose anti-platelet therapy (ex. Plavix 150mg)^2 Myocardial infarction or unstable angina within 6 or 1 month of starting nintedanib treatment, respectively

• Known inherited predisposition to thrombosis

• Patient with a history of a thrombotic event within 12 months of starting nintedanib treatment

• Known predisposition to bleeding

• Patients with severe hepatic impairment

• History of a gastrointestinal perforation

Related Conditions & MeSH terms

• Lung Cancer
• Lung Metastases
• Pneumonia
• Radiation Pneumonitis

Intervention

Drug:
• Nintedanib

• Prednisone

Other:
• Placebo

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network (Data Collection Only)	Allentown	Pennsylvania
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Brigham and Women's Hospital (Data Collection Only)	Boston	Massachusetts
United States	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	MD ANDERSON CANCER CENTER (Data Collection Only)	Houston	Texas
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York
United States	Myriad Genetic Laboratory (Data or Specimen Analysis Only)	Salt Lake City	Utah
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who are free from pulmonary exacerbations	An acute exacerbation will be defined as (all criteria must be met): Unexplained worsening or development of cough, dyspnea, hypoxia, or pneumonitis lasting more than 4 days; New or worsening diffuse pulmonary infiltrates on chest CT (with or without contrast) or new high resolution CT parenchymal abnormalities without significant pneumothorax or pleural effusion	12 months

External Links

•   Memorial Sloan Kettering Cancer Center