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

Official title

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

Overview

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

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

1. 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. 2. 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. 3. 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. 4. 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

Interventions

• 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.

Primary outcome measures

• 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.]
• 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.]

Secondary outcome measures (12)

• Lung cancer-associated symptoms assessment [Time frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.]
• Treatment-related side effects in lung cancer [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.]
• Respiratory symptoms evaluation using St. George respiratory questionnaire [Time frame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.]
• 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.]
• Pulmonary function evaluation using spirometry test [Time frame: 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). [Time frame: 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) [Time frame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Mexico · 2 centers

• Instituto Nacional de Cancerologia — Mexico City
• Instituto Nacional de Enfermedades Respiratorias — Mexico City

Publications

• Arrieta O, Guzman-de Alba E, Alba-Lopez LF, Acosta-Espinoza A, Alatorre-Alexander J, Alexander-Meza JF, Allende-Perez SR, Alvarado-Aguilar S, Araujo-Navarrete ME, Argote-Greene LM, Aquino-Mendoza CA, Astorga-Ramos AM, Austudillo-de la Vega H, Aviles-Salas A, Barajas-Figueroa LJ, Barroso-Quiroga N, Blake-Cerda M, Cabrera-Galeana PA, Calderillo-Ruiz G, Campos-Parra AD, Cano-Valdez AM, Capdeville-Gar PMID 24459776
• Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, Ewing M, Abdulrahman R, DesRosiers C, Williams M, Fletcher J. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol. 2006 Oct 20;24(30):4833-9. doi: 10.1200/JCO.2006.07.5937. PMID 17050868
• Henkenberens C, Janssen S, Lavae-Mokhtari M, Leni K, Meyer A, Christiansen H, Bremer M, Dickgreber N. Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade II after radiotherapy - a single-centre experience. Radiat Oncol. 2016 Feb 2;11:12. doi: 10.1186/s13014-016-0580-3. PMID 26830686
• Kim S, Oh IJ, Park SY, Song JH, Seon HJ, Kim YH, Yoon SH, Yu JY, Lee BR, Kim KS, Kim YC. Corticosteroid therapy against treatment-related pulmonary toxicities in patients with lung cancer. J Thorac Dis. 2014 Sep;6(9):1209-17. doi: 10.3978/j.issn.2072-1439.2014.07.16. PMID 25276362
• Ding NH, Li JJ, Sun LQ. Molecular mechanisms and treatment of radiation-induced lung fibrosis. Curr Drug Targets. 2013 Oct;14(11):1347-56. doi: 10.2174/13894501113149990198. PMID 23909719
• Williams JP, Johnston CJ, Finkelstein JN. Treatment for radiation-induced pulmonary late effects: spoiled for choice or looking in the wrong direction? Curr Drug Targets. 2010 Nov;11(11):1386-94. doi: 10.2174/1389450111009011386. PMID 20583979
• Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic index. Br J Clin Pharmacol. 2015 Sep;80(3):372-80. doi: 10.1111/bcp.12637. Epub 2015 May 28. PMID 25808113
• Leach C, Colice GL, Luskin A. Particle size of inhaled corticosteroids: does it matter? J Allergy Clin Immunol. 2009 Dec;124(6 Suppl):S88-93. doi: 10.1016/j.jaci.2009.09.050. PMID 19962042

Identifiers

NCT: NCT03803787 · CI/910/17

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗