Clinical trial NCT03803787: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Radiation Pneumonitis
Keywords: 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
Lead sponsor: Instituto Nacional de Cancerologia de Mexico
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Enfermedades Respiratorias
First posted: 2019-01-15
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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

Primary outcomes:
measure: Pneumonitis graded by the Common terminology criteria for adverse event v4.0. (CTCAE v4.0).
timeFrame: from the beginning of radiotherapy up to 1 year after the 1st session.
measure: Pneumonitis graded by the Radiation Therapy Oncology Group score (RTOG)
timeFrame: from the beginning of radiotherapy up to 1 year after the 1st session.
Secondary outcomes:
measure: Lung cancer-associated symptoms assessment
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Treatment-related side effects in lung cancer
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Cognitive functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Emotional Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment
measure: Physical functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Role Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Social Functioning evaluated by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Respiratory symptoms evaluation using St. George respiratory questionnaire
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Dyspnea assessment by the Borg Scale Dyspnea Index (BSDI)
timeFrame: before the start Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Pulmonary function evaluation using spirometry test
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment
measure: Pulmonary function evaluation using diffusion lung capacity of carbon monoxide measurement (DLCO).
timeFrame: before the start of Radiotherapy and at 6, 12, 24 and 48-weeks post-treatment.
measure: Airway inflammatory response evaluation using the fraction of exhaled nitric oxide measurement (FeNO)
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
measure: Pulmonary function evaluation using Impulse oscillometry test (IOS)
timeFrame: before the start of Radiotherapy, and at 6, 12, 24 and 48-weeks post-treatment.
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Mexico City
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias
Study officials:
affiliation: Instituto Nacional de Cancerologia, Mexico
name: Oscar Arrieta, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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-Garcia D, Castillo-Ortega G, Casillas-Suarez C, Castillo-Gonzalez P, Corona-Cruz JF, Correa-Acevedo ME, Cortez-Ramirez SS, de la Cruz-Vargas JA, de la Garza-Salazar JG, de la Mata-Moya MD, Dominguez-Flores ME, Dominguez-Malagon HR, Dominguez-Parra LM, Dominguez-Peregrina A, Duran-Alcocer J, Enriquez-Aceves MI, Elizondo-Rios A, Escobedo-Sanchez MD, de Villafranca PE, Flores-Cantisani A, Flores-Gutierrez JP, Franco-Marina F, Franco-Gonzalez EE, Franco-Topete RA, Fuentes-de la Pena H, Galicia-Amor S, Gallardo-Rincon D, Gamboa-Dominguez A, Garcia-Andreu J, Garcia-Cuellar CM, Garcia-Sancho-Figueroa MC, Garcia-Torrentera R, Gerson-Cwilich R, Gomez-Gonzalez A, Green-Schneeweiss L, Guillen-Nunez Mdel R, Gutierrez-Velazquez H, Ibarra-Perez C, Jimenez-Fuentes E, Juarez-Sanchez P, Juarez-Ramiro A, Kelly-Garcia J, Kuri-Exsome R, Lazaro-Leon JM, Leon-Rodriguez E, Llanos-Osuna S, Llanos-Osuna S, Loyola-Garcia U, Lopez-Gonzalez JS, Lopez y de Antunano FJ, Loustaunau-Andrade MA, Macedo-Perez EO, Machado-Villarroel L, Magallanes-Maciel M, Martinez-Barrera L, Martinez-Cedillo J, Martinez-Martinez G, Medina-Esparza A, Meneses-Garcia A, Mohar-Betancourt A, Morales Blanhir J, Morales-Gomez J, Motola-Kuba D, Najera-Cruz MP, Nunez-Valencia Cdel C, Ocampo-Ocampo MA, Ochoa-Vazquez MD, Olivares-Torres CA, Palomar-Lever A, Patino-Zarco M, Perez-Padilla R, Pena-Alonso YR, Perez-Romo AR, Aquilino Perez M, Pinaya-Ruiz PM, Pointevin-Chacon MA, Poot-Braga JJ, Posadas-Valay R, Ramirez-Marquez M, Reyes-Martinez I, Robledo-Pascual J, Rodriguez-Cid J, Rojas-Marin CE, Romero-Bielma E, Rubio-Gutierrez JE, Saenz-Frias JA, Salazar-Lezama MA, Sanchez-Lara K, Sansores Martinez R, Santillan-Doherty P, Alejandro-Silva J, Tellez-Becerra JL, Toledo-Buenrostro V, Torre-Bouscoulet L, Torecillas-Torres L, Torres M, Tovar-Guzman V, Turcott-Chaparro JG, Vazquez-Cortes JJ, Vazquez-Manriquez ME, Vilches-Cisneros N, Villegas-Elizondo JF, Zamboni MM, Zamora-Moreno J, Zinser-Sierra JW. [National consensus of diagnosis and treatment of non-small cell lung cancer]. Rev Invest Clin. 2013 Mar;65 Suppl 1:S5-84. Spanish.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Bledsoe TJ, Nath SK, Decker RH. Radiation Pneumonitis. Clin Chest Med. 2017 Jun;38(2):201-208. doi: 10.1016/j.ccm.2016.12.004. Epub 2017 Mar 1.
citation: Simone CB 2nd. Thoracic Radiation Normal Tissue Injury. Semin Radiat Oncol. 2017 Oct;27(4):370-377. doi: 10.1016/j.semradonc.2017.04.009.
citation: Vallard A, Rancoule C, Le Floch H, Guy JB, Espenel S, Le Pechoux C, Deutsch E, Magne N, Chargari C. [Medical prevention and treatment of radiation-induced pulmonary complications]. Cancer Radiother. 2017 Aug;21(5):411-423. doi: 10.1016/j.canrad.2017.03.004. Epub 2017 Jun 5. French.