Nintedanib and Prednisone in Reducing Radiation-Induced Pneumonitis in Patients with Lymphoma, Chest, or Breast Cancer or Lung Metastases

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
• Prior treatment with thoracic radiotherapy completed > 4 weeks and =< 9 months prior to enrollment
• Radiographic evidence of radiation pneumonitis on a computed tomography (CT) scan of the chest with or without contrast
• Newly diagnosed clinical grade 2 or higher radiation pneumonitis according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria
• Age >= 18 years
• Written informed consent signed prior to entry into the study
• Karnofsky performance status (KPS) >= 70 %
• Reduction of any acute toxicity from radiation treatment to grade 1

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
• Aspartate aminotransferase (AST) > 1.5 X upper limit of normal (ULN), alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN)
• Bilirubin > 1.5 X ULN
• >= grade 2 proteinuria
• Creatinine > 1.5 x ULN
• Glomerular filtration rate (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 enrollment * Patients will be considered to be of childbearing potential unless surgical sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years; women of childbearing potential who are sexually active and not using a highly effective method of birth control before the trial for at least one month, during the trial, and for at least three months after the end of active therapy are not allowed to participate in the trial; a highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomized partner
• 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
• International normalized ratio (INR) > 2
• Prothrombin time (PT) and partial thromboplastin time (PTT) > 1.5 x 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
• Absolute neutrophil count (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 150 mg)
• 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