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

• ClinicalTrials.gov Identifier: NCT02496585
• Recruitment Status: Completed
• First Posted: July 14, 2015
• Last Update Posted: April 16, 2024
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Boehringer Ingelheim
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: July 9, 2015
• First Posted Date: July 14, 2015
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: July 8, 2015
• Actual Primary Completion Date: April 12, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2016)

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

Original Primary Outcome Measures (submitted: July 13, 2015)

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 or new high resolution CT parenchymal abnormalities without significant pneumothorax or pleural effusion

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Nintedanib (BIBF 1120) + Prednisone Taper in Patients With Radiation Pneumonitis
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Lung Cancer
• Lung Metastases

Intervention

• Drug: Nintedanib
  Other Name: BIBF 1120
• Drug: Prednisone
• Other: Placebo

Study Arms

• Experimental: 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).
  Interventions:

  • Drug: Nintedanib
  • Drug: Prednisone
• Experimental: 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).
  Interventions:

  • Drug: Prednisone
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: July 8, 2020): 33
• Original Estimated Enrollment (submitted: July 13, 2015): 68
• Actual Study Completion Date: April 12, 2024
• Actual Primary Completion Date: April 12, 2024 (Final data collection date for primary outcome measure)

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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02496585
• Other Study ID Numbers: 14-167
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Boehringer Ingelheim

Investigators

• Principal Investigator: Zachary Moore, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: April 2024