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

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