Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prophylactic Inhaled Steroids to Reduce Radiation Pneumonitis Frequency and Severity in Lung Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03803787
Recruitment Status : Recruiting
First Posted : January 15, 2019
Last Update Posted : January 16, 2019
Sponsor:
Collaborator:
Instituto Nacional de Enfermedades Respiratorias
Information provided by (Responsible Party):
Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico

Tracking Information
First Submitted Date  ICMJE January 3, 2019
First Posted Date  ICMJE January 15, 2019
Last Update Posted Date January 16, 2019
Actual Study Start Date  ICMJE September 1, 2018
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Pneumonitis graded by the Common terminology criteria for adverse event v4.0. (CTCAE v4.0). [ Time Frame: from the beginning of radiotherapy up to 1 year after the 1st session. ]
    Current score for radiation pneumonitis according to symptoms and radiographic changes. Grade 0: No changes, Grade 1: Asymptomatic or mild respiratory symptoms, Grade 2: Moderate respiratory symptoms of pneumonitis (a severe cough) and radiographic changes (radiographic patches), Grade 3: Severe respiratory symptoms of pneumonitis, dense radiographic changes. Grade 4: Symptoms of acute respiratory failure requiring assisted ventilation or continuous oxygen. Grade 5: Death directly related to late effects of radiotherapy.
  • Pneumonitis graded by the Radiation Therapy Oncology Group score (RTOG) [ Time Frame: from the beginning of radiotherapy up to 1 year after the 1st session. ]
    Current score for radiation pneumonitis according to symptoms and radiographic changes. Grade 0: No changes, Grade 1: Asymptomatic, only radiological or tomographic findings, Grade 2: Symptomatic, does not interfere with daily activities, Grade 3: Symptomatic, interferes with daily activities, requires supplemental oxygen. Grade 4: Threatens life, needing ventilator support. Grade 5: Severe pneumonitis with fatal outcome.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Lung cancer-associated symptoms assessment [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    Symptoms are evaluated with the supplementary lung cancer-specific questionnaire of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (validated Mexican-Spanish version). It comprises 13 questions related to the assessment of dyspnoea, pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that scores range from 0 to 100. A higher scale score represents a higher level of symptoms.
  • Treatment-related side effects in lung cancer [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    Symptoms are evaluated with the supplementary lung cancer-specific questionnaire of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (validated Mexican-Spanish version). It comprises 13 questions related to the assessment of dyspnoea, pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that scores range from 0 to 100. A higher scale score represents a higher level of side-effects.
  • Cognitive functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    The cognitive functioning is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires. It comprises two questions related to the assessment of short and long-term memory. The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that scores range from 0 to 100. A higher scale score represents a healthy level of functioning.
  • Emotional Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment ]
    The Emotional Functioning is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires. It comprises four questions related to the assessment of depression, anxiety, irritability, and stress. The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that the scores range from 0 to 100. A higher scale score represents a represents a healthy level of functioning.
  • Physical functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    The Physical functioning is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires. It comprises five questions related to self-sufficiency activities (eating, walking, laying in bed or completing simple chores). The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that the scores range from 0 to 100. A higher scale score represents a represents a healthy level of functioning.
  • Role Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    The Role functioning is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires. It comprises two questions related to daily activities (work and hobbies limitation). The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that the scores range from 0 to 100. A higher scale score represents a represents a healthy level of functioning.
  • Social Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    The Social Functioning is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires. It comprises two questions related to family life and social activities. The items scale ranges from 1 (Not at all) to 4 (Very much). The average of the items that contribute to the scale (raw score) is estimated and transformed so that the scores range from 0 to 100. A higher scale score represents a represents a healthy level of functioning.
  • Respiratory symptoms evaluation using St. George respiratory questionnaire [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    Respiratory symptoms are evaluated using the St. George respiratory questionnaire validated to Mexican-Spanish version. It is a disease-specific instrument designed to measure the impact on overall health, daily life, and perceived well-being in patients with airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.
  • Dyspnea assessment by the Borg Scale Dyspnea Index (BSDI) [ Time Frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    A system used to document the severity of the patient's shortness of breath using numbers anchored with verbal descriptions. This scale asks the patient to rate the dyspnea. It starts at number 0 where the breathing is causing no difficulty at all and progresses through to number 10 where the breathing difficulty is maximal.
  • Pulmonary function evaluation using spirometry test [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment ]
    Spirometry measures the inhaled and exhaled air volume as a function of time using a forced expiratory maneuver.
  • Pulmonary function evaluation using diffusion lung capacity of carbon monoxide measurement (DLCO). [ Time Frame: before the start of Radiotherapy and at 6, 12, 24 and 48-weeks post-treatment. ]
    Diffusion lung capacity of carbon monoxide (DLCO) test measures the conductance of gas transfer from inspired gas to the red blood cells.
  • Airway inflammatory response evaluation using the fraction of exhaled nitric oxide measurement (FeNO) [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    Nitric oxide concentration detected in the exhaled gas by chemiluminescence reported as particles per million.
  • Pulmonary function evaluation using Impulse oscillometry test (IOS) [ Time Frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. ]
    Impulse oscillometry provides a rapid, noninvasive measure of airway impedance during normal tidal breathing.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prophylactic Inhaled Steroids to Reduce Radiation Pneumonitis Frequency and Severity in Lung Cancer Patients
Official Title  ICMJE Prophylactic Inhaled Steroids to Reduce Radiation Pneumonitis Frequency and Severity in Non-small Cell Lung Cancer Patients
Brief Summary Thoracic lung cancer treatment often induces lung toxicity as an adverse effect of concomitant therapy (CCRT) using chemo or target therapy drugs in addition to radiation therapy, in non-small cell lung cancer (NSCLC) patients with advanced disease. The presence of Pneumonitis is the most severe acute lung injury derived from this intervention. Pneumonitis might evolve to respiratory failure and even death, with a high incidence in the investigator's population (50%) as reported in different studies. Its prevention with different immunomodulatory targets has not succeeded. The use of inhaled steroids is used in various pathologies such as Asthma and Chronic Obstructive Pulmonary Disease (COPD) to reduce the airway inflammatory response. The advantage of using inhaled corticosteroids as opposed to orally administered drugs bases in the low incidence of systemic side effects and the fact that its use does not require tapering. Currently, the effectiveness of using prophylactic inhaled steroids for reducing the incidence of CCRT-induced pneumonitis and its impact regarding the quality of life has not been demonstrated in a clinical trial.
Detailed Description

Pneumonitis is the most common entity within the spectrum of treatment-induced lung injuries, which can progress to irreversible pulmonary fibrosis. In the last year, the prevalence registered at the National Cancer Institute in Mexico increased up to 70% in those who receive radiotherapy (RT), increasing symptoms and reducing lung function, quality of life and survival.

Since the development of pneumonitis is multifactorial, it has not been possible to identify or reduce the risks of presenting lung injury. However, many studies have been conducted in search of prognostic and preventable risk factors. At the moment, there is no preventive treatment that reduces the severity of the presentation of the disease. Several publications have described the loss of lung function after RT secondary to lung parenchyma injury adjacent to the radiation site.

Currently, the benefit of prophylactic treatment with inhaled steroids in patients receiving RT is unknown. We expect that its use protects against the onset of pneumonitis or decreases the degree of lung inflammation after the administration of concomitant chemo or target therapy and radiotherapy treatment (CCRT). The improvement in the patient's respiratory symptomatology and lung function reflects the reduction in the degree of inflammation. With this work, the investigators intend to demonstrate a decrease in the incidence of treatment-related pneumonitis, an increase in survival and quality of life without modifying the response to treatment with the use of inhaled steroids.

Methods: It is a randomized clinical trial assessing the effect of prophylactic inhaled Budesonide in the prevention of the development of pneumonitis in non-small cell lung cancer (NSCLC) patients with unresectable stage III/IV tumors, who receive CCRT with chemotherapy or targeted drugs and thoracic radiation. Patients are recruited in the Lung Cancer Unit at the National Cancer Institute in Mexico. They are stratified according to the given treatment (chemo plus RT or targeted drugs plus RT) and randomized to the control group (without intervention) or the experimental group (use of inhaled Budesonide at 400 mcg given twice a day) and followed for one year. Demographic, biochemical, lung function (spirometry with bronchodilator inhaler, Diffusion lung capacity measurement, Fraction of exhaled nitric oxide measurement and impulse oscillometry), quality of life and respiratory symptoms variables are evaluated at baseline, at 6, 12, 24 and 48-weeks post-RT. The patients in the experimental group receive an inhaler monthly and a diary to register its use at every control visit. The presence of symptoms and computed tomography evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) identify the development of Pneumonitis.

Sample size: To determine the sample size, the investigators considered the proportion of patients with radiation pneumonitis reported in the literature (0.7) and the percentage of patients with pneumonitis that required systemic corticosteroids treatment (0.27). It requires 31 patients at the inhaled Budesonide group and in the control group, plus 20% of loss gives us a total of 36 patients per group, with a power of 90% and an α of 0.05.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Radiation Pneumonitis
Intervention  ICMJE Drug: Inhaled budesonide
Patients will use inhaled budesonide (Numark) with space chamber at 400 mcg given twice daily initiating after the first dose of RT and continuing until pneumonitis development or 12 months completed.
Other Name: Numark
Study Arms  ICMJE
  • Experimental: QT/RT + Budesonide
    Patients are receiving chemotherapy (QT) and radiotherapy (RT) plus inhaled Budesonide with space chamber at 400 mcg given twice daily initiating after the first dose of RT and continuing until pneumonitis development or 12 months completed.
    Intervention: Drug: Inhaled budesonide
  • No Intervention: QT/RT + No medication
    Patients are receiving chemotherapy (QT) and radiotherapy (RT) without intervention therapy and followed during 12 months.
  • Experimental: Target drug/RT + Budesonide
    Patients are receiving target therapy and radiotherapy (RT) plus inhaled Budesonide with space chamber at 400 mcg given twice daily initiating after the first dose of RT and continuing until pneumonitis development or 12 months completed.
    Intervention: Drug: Inhaled budesonide
  • No Intervention: Target drug/RT + No medication
    Patients are receiving target treatment and radiotherapy (RT) without intervention therapy and followed during 12 months.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2019)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with non-small cell lung cancer (NSCLC) with unresectable locally advanced or metastatic disease (IIIA, IIIB or IV) of the classification tumor node, metastasis (TNM) of malignant lung tumors, 7th edition.
  • NSCLC patients candidates for concomitant treatment (chemotherapy plus radiotherapy or target therapy plus radiotherapy).
  • Evidence of measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, Karnofsky 70-100.
  • Life expectancy of > 4 months at the time of screening
  • Patients with the ability to comply with the study and follow-up procedures.
  • Patients with previous surgery less than four weeks.
  • Must be willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the protocol tests and procedures.

Exclusion Criteria:

  • Unstable systemic disease: active infection, heart, liver, kidney or metabolic disease; including uncontrolled chronic lung disease.
  • Patients treated with systemic or inhaled corticosteroids.
  • Patients of reproductive age without a family planning method, pregnant or lactating.
  • Previous diagnosis of Pneumonitis with toxicity grade ≥ 2 by CTCAE v4.0 or RTOG scale.
  • Patients with disease progression.
  • Inspiratory flow < 90 liters / min.
  • Discontinue of Treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Oscar Arrieta, MD MSc 015556280400 ext 71100 ogarrieta@gmail.com
Contact: Diana Flores 015556280400 ext 71101 clinicacancerpulmonincan@gmail.com
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03803787
Other Study ID Numbers  ICMJE CI/910/17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data of the participants will be reported in the publication results.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: october 2021
Access Criteria: the information will be available after being published in an indexed journal, any information or data related to this study must be requested via e-mail with the researchers.
Responsible Party Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico
Study Sponsor  ICMJE Instituto Nacional de Cancerologia de Mexico
Collaborators  ICMJE Instituto Nacional de Enfermedades Respiratorias
Investigators  ICMJE
Principal Investigator: Oscar Arrieta, MD MSc Instituto Nacional de Cancerologia, Mexico
PRS Account Instituto Nacional de Cancerologia de Mexico
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP