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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lung Cancer, Lung Metastases

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Prednisone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nintedanib + Prednisone<br>The initial dose of nintedanib will be 150mg two times per day orally according to study protocol. Nintedanib will be taken for 12 weeks. Patients will be given a prednisone taper (40mg prednisone daily for 2 weeks, followed by a strict dose taper of 10mg every 2 weeks for 4 weeks, followed by 10mg for one week and 5mg for one week, for a total duration on prednisone of 8 weeks). | Drug: Nintedanib<br> <br> * Other names: BIBF 1120;Drug: Prednisone<br> <br> |
| Experimental: Placebo + Prednisone<br>Placebo will be taken for 12 weeks. Patients will be given a prednisone taper (40mg prednisone daily for 2 weeks, followed by a strict dose taper of 10mg every 2 weeks for 4 weeks, followed by 10mg for one week and 5mg for one week, for a total duration on prednisone of 8 weeks). | Drug: Prednisone<br> <br> Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nintedanib (BIBF 1120), Prednisone, Radiation Pneumonitis