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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02496585

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Locations

Arms

Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Lung Metastases	Drug: Nintedanib Drug: Prednisone Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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).	Drug: Nintedanib Other Names: BIBF 1120 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).	Drug: Prednisone Other: Placebo

Arm

Intervention/Treatment

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).

Drug: Nintedanib

Other Names:

BIBF 1120

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).

Drug: Prednisone

Other: Placebo

Outcome Measures

Primary Outcome Measures

Number of patients who are free from pulmonary exacerbations [12 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital (Data Collection Only)	Boston	Massachusetts	United States	02115
2	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States	07920
3	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
4	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
5	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
6	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
9	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
10	Lehigh Valley Health Network (Data Collection Only)	Allentown	Pennsylvania	United States	18103
11	MD ANDERSON CANCER CENTER (Data Collection Only)	Houston	Texas	United States	77030
12	Myriad Genetic Laboratory (Data or Specimen Analysis Only)	Salt Lake City	Utah	United States	84108