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

Study Overview
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Brief Summary
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This randomized clinical study aims to assess whether prophylactic treatment with inhaled steroids in patients with locally advanced or concomitantly treated non-small cell lung carcinoma who are candidates for combination treatment with QT/RT or IMT + QT/RT. The main questions it aims to answer are: Whether prophylactic treatment decreases the severity of NPR on CTCAE v4.0 and RTOG scales. Whether inhaled steroid use modifies the response to radiation therapy treatment compared to patients who do not receive prophylactic inhaled steroids.

Detailed Description
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Clinical evaluation The following BASELINE data shall be taken prior to radiation therapy: Demographic, clinical, laboratory, and imaging data will be obtained from medical history and electronic records. The patient will be instructed to perform the PFRs and tests of lung function. Two EORTC, QLQ-C30, and QLQ LC13 quality of life questionnaires and three respiratory symptom questionnaires (St. George, dyspnea scale, and modified BORG) will be performed on the same day of lung function tests. Additionally; blood samples will be taken for the evaluation of inflammatory mediators at the following times: BASAL (before RT), and every six weeks up to 48 weeks post-RT. INTERVENTION GROUP Prior to the onset of RT, the patient will be sorted to receive the control rather than experimental intervention (QT/RT or IMT + QT/RT) and a logbook to record adherence to treatment. An IDM device shall be granted per month, containing the number of doses corresponding to 30 days. The record in the database of the day of the first session of RT will be taken to quantify the number of days of use of the drug and grant the next device per 30 days until the end of the study. The patient will be instructed on the use of the device inhaled with the spacer chamber in the clinic Pulmonology consultation, alarm data and indications of the use of the drug will be given in writing, and knowledge will be reinforced at each visit. The patient will be granted the drug use log where the patient will place the date and time of use of the drug to assess adherence to treatment

Official Title
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Prophylactic Inhaled Steroids to Reduce Radiation Pneumonitis Frequency and Severity in Non-small Cell Lung Cancer Patients

Conditions
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Radiation Pneumonitis

Intervention / Treatment
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* Drug: Inhaled budesonide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QT/RT + Budesonide<br>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. | Drug: Inhaled budesonide<br>* 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.<br>* Other names: Numark;|
| No Intervention: QT/RT + No medication<br>Patients are receiving chemotherapy (QT) and radiotherapy (RT) without intervention therapy and followed during 12 months. | |
| Experimental: Target drug/RT + Budesonide<br>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. | Drug: Inhaled budesonide<br>* 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.<br>* Other names: Numark;|
| No Intervention: Target drug/RT + No medication<br>Patients are receiving target treatment and radiotherapy (RT) without intervention therapy and followed during 12 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pneumonitis graded by the Common terminology criteria for adverse event v4.0. (CTCAE v4.0). | 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. | from the beginning of radiotherapy up to 1 year after the 1st session. | 
| Pneumonitis graded by the Radiation Therapy Oncology Group score (RTOG) | 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. | from the beginning of radiotherapy up to 1 year after the 1st session. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung cancer-associated symptoms assessment | 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. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Treatment-related side effects in lung cancer | 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. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Cognitive functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire | 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. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Emotional Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment | 
| Physical functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Role Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Social Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Respiratory symptoms evaluation using St. George respiratory questionnaire | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Dyspnea assessment by the Borg Scale Dyspnea Index (BSDI) | 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. | before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Pulmonary function evaluation using spirometry test | Spirometry measures the inhaled and exhaled air volume as a function of time using a forced expiratory maneuver. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment | 
| Pulmonary function evaluation using diffusion lung capacity of carbon monoxide measurement (DLCO). | Diffusion lung capacity of carbon monoxide (DLCO) test measures the conductance of gas transfer from inspired gas to the red blood cells. | before the start of Radiotherapy and at 6, 12, 24 and 48-weeks post-treatment. | 
| Airway inflammatory response evaluation using the fraction of exhaled nitric oxide measurement (FeNO) | Nitric oxide concentration detected in the exhaled gas by chemiluminescence reported as particles per million. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 
| Pulmonary function evaluation using Impulse oscillometry test (IOS) | Impulse oscillometry provides a rapid, noninvasive measure of airway impedance during normal tidal breathing. | before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, Radiation Pneumonia, Lung cancer treatment, Respiratory Tract Neoplasms, Radiation fibrosis, Thoracic Neoplasms, Lung Diseases, Radiation Injury with Fibrosis, Radiation Fibrosis of Lung, Lung Injury