Glutamine Plus L. Reuteri Prevents TKI Therapy-diarrhea in Patients With NSCLC

Study Overview
=================
Brief Summary
-----------------
This open-label randomized clinical trial aims to evaluate the glutamine plus Lactobacillus reuteri supplementation effect in a standard-of-care diet in EGFR mutant patients with advanced non-small cell lung cancer (NSCLC) under tyrosine kinase inhibitors (TKIs) therapy. The main question it aims to answer is ¿What is the effect of glutamine plus L. reuteri added to an astringent diet in preventing diarrhea generated by TKI therapy? Patients will receive an astringent diet supplemented with 10 grams of glutamine and L. reuteri (100 million CFU). Researchers will compare the Glutamine plus L. reuteri diet with a standard astringent diet to see if TKI therapy diarrhea is prevented.

Detailed Description
-----------------
Patients in the experimental group will receive two sachets of Glutapak-R every twelve hours for up to six weeks alongside treating physician-chosen EGFR therapy. Patients in the control group will receive a standard-of-care diet. All patients will receive nutritional counseling every two weeks.

Official Title
-----------------
Effect of Glutamine Plus Lactobacillus Reuteri Added to an Astringent Diet in Preventing Diarrhea Caused by Tyrosine Kinase Inhibitors (TKIs) in Patients With Advanced Non-small Cell Lung Cancer

Conditions
-----------------
Non-Small Cell Lung Cancer With EGFR Mutation

Intervention / Treatment
-----------------
* Combination Product: Glutamine plus L. reuteri


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Both sexes ≥ 18 years old Pathologically confirmed diagnosis of NSCLC Stage IIIB - IV by the American Joint Committee of Cancer Version 8. Candidates to receive EGFR-TKI treatment (1st & 2nd generation TKI) ECOG score ≤ 2 Life expectancy > eight weeks Signed written informed consent Exclusion Criteria: Patients who cannot attend the first protocol appointment. Treatment with other anti-cancer therapy Participating in other clinical trials in the former four weeks Any other serious condition or uncontrolled active infection, altered mental status or psychiatric disorder that, in the investigator´s opinion, would limit the ability of an individual to meet the requirements of the study or which affects the interpretability of the results. Active hepatitis virus infection (any serotype) or chronic infection with a potential risk of reactivation evaluated through a serological panel. Active HIV infection. Breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with Non-Small Cell Lung Cancer and EGFR Mutation receiving first or second generation-TKI therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention diet<br>Astringent diet supplemented with one sachet containing 10 grams of glutamine plus 100 million Colony Forming Units (CFU) of Lactobacillus reueri every 12 hours, from baseline treatment up to 6 weeks or death. | Combination Product: Glutamine plus L. reuteri<br>* Glutamine plus Lactobacillus reueri twice daily for up to 6 weeks or death<br>* Other names: Glutapak-R;|
| No Intervention: Standard diet<br>Astringent diet from baseline treatment up to 6 weeks or death. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diarrhea toxicity | The diarrhea grade will be determined from 1 to 5 following the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. As shown below: grade 1: Increase of < 4 stools per day over baseline; mild increase in ostomy output compared to baseline grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL. grade 3: Increase of >= 7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care ADL. grade 4: Life-threatening consequences; urgent intervention indicated grade 5: Death | every two weeks, from first dose of TKI therapy up to six weeks. | 
| Functional Assessment of Chronic Illness Therapy | This assessment will be evaluated with a specific scale for diarrhea (FACIT instrument), which consists of 11 items that assign a value of 0 to 4 for each one. Higher the score, the better quality of life related to diarrhea. | Every two weeks, from first dose of TKI therapy up to six weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade of gastrointestinal toxicity | This outcome will be determined from grades 1 to 5 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for gastrointestinal disorders. | Every two weeks, from first dose of TKI therapy up to six weeks. | 
| Measurement of health related quality of life (QoL) | The QoL of patients with cancer will be determined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30 v3.0) instrument. | Every two weeks, from first dose of TKI therapy up to six weeks. | 
| Measurement of quality of life (QoL) for lung cancer patients | The QoL for Lung Cancer patients will be determined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC QLQ-LC13) instrument. | Every two weeks, from first dose of TKI therapy up to six weeks. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-Small Cell Lung Cancer, EGFR mutation, Glutamine, Lactobacillus reuteri, standard-care diet