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
Overview
- Phase
- Phase 2
- Intervention
- Nintedanib
- Conditions
- Lung Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 34
- Locations
- 12
- Primary Endpoint
- Number of Patients Who Are Free From Pulmonary Exacerbations
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Nintedanib + Prednisone
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).
Intervention: Nintedanib
Nintedanib + Prednisone
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).
Intervention: Prednisone
Placebo + Prednisone
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).
Intervention: Prednisone
Placebo + Prednisone
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).
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Patients Who Are Free From Pulmonary Exacerbations
Time Frame: 12 months
An acute exacerbation will be defined as (all criteria must be met): 1. Unexplained worsening or development of cough, dyspnea, hypoxia, or pneumonitis lasting more than 4 days 2. 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