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

Primary Purpose

Lung Cancer, Lung Metastases

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nintedanib
Prednisone
Placebo
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Nintedanib (BIBF 1120), Prednisone, Radiation Pneumonitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Brigham and Women's Hospital (Data Collection Only)
  • Memorial Sloan Kettering Cancer Center at Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Cancer Center @ Suffolk
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering at Mercy Medical Center
  • Memorial Sloan Kettering Nassau
  • Lehigh Valley Health Network (Data Collection Only)
  • MD ANDERSON CANCER CENTER (Data Collection Only)
  • Myriad Genetic Laboratory (Data or Specimen Analysis Only)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Nintedanib + Prednisone

Placebo + Prednisone

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 9, 2015
Last Updated
July 21, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT02496585
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Lung Metastases
Keywords
Nintedanib (BIBF 1120), Prednisone, Radiation Pneumonitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nintedanib + Prednisone
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo + Prednisone
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Nintedanib
Other Intervention Name(s)
BIBF 1120
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of patients who are free from pulmonary exacerbations
Description
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
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Rimner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital (Data Collection Only)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center @ Suffolk
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering at Mercy Medical Center
City
Rockville Centre
State/Province
New York
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
Lehigh Valley Health Network (Data Collection Only)
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
MD ANDERSON CANCER CENTER (Data Collection Only)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Myriad Genetic Laboratory (Data or Specimen Analysis Only)
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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