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

Non-Small Cell Lung Cancer With EGFR Mutation Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05852990
• Other study ID #: CEI/1565/21 INCAN/CEI/0074/22
• Status: Recruiting
• Phase: Phase 3
• Start date: March 1, 2022
• Est. completion date: December 12, 2023

Study information

• Verified date: May 2023
• Source: Instituto Nacional de Cancerologia de Mexico
• Contact: Oscar G Arrieta Rodriguez, M.D., M.Sc.
• Phone: 556280400
• Email: ogar[@]unam.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: December 12, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Diarrhea
• Lung Neoplasms
• Non-Small Cell Lung Cancer With EGFR Mutation

Intervention

Combination Product:
• Glutamine plus L. reuteri
Glutamine plus Lactobacillus reueri twice daily for up to 6 weeks or death

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerologia de Mexico	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancerologia de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (7)

Achamrah N, Dechelotte P, Coeffier M. Glutamine and the regulation of intestinal permeability: from bench to bedside. Curr Opin Clin Nutr Metab Care. 2017 Jan;20(1):86-91. doi: 10.1097/MCO.0000000000000339. — View Citation

Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010 Feb 21;10:50. doi: 10.1186/1471-2407-10-50. — View Citation

Arrieta O, Nunez-Valencia C, Reynoso-Erazo L, Alvarado S, Flores-Estrada D, Angulo LP, Onate-Ocana LF. Health-related quality of life in patients with lung cancer: validation of the Mexican-Spanish version and association with prognosis of the EORTC QLQ-LC13 questionnaire. Lung Cancer. 2012 Jul;77(1):205-11. doi: 10.1016/j.lungcan.2012.02.005. Epub 2012 Mar 3. — View Citation

Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG, Shepherd FA. Non-small-cell lung cancer. Lancet. 2011 Nov 12;378(9804):1727-40. doi: 10.1016/S0140-6736(10)62101-0. Epub 2011 May 10. — View Citation

Sanchez-Lara K, Turcott JG, Juarez E, Guevara P, Nunez-Valencia C, Onate-Ocana LF, Flores D, Arrieta O. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer. 2012;64(4):526-34. doi: 10.1080/01635581.2012.668744. Epub 2012 Apr 10. — View Citation

Secombe KR, Van Sebille YZA, Mayo BJ, Coller JK, Gibson RJ, Bowen JM. Diarrhea Induced by Small Molecule Tyrosine Kinase Inhibitors Compared With Chemotherapy: Potential Role of the Microbiome. Integr Cancer Ther. 2020 Jan-Dec;19:1534735420928493. doi: 10.1177/1534735420928493. — View Citation

Walters S, Maringe C, Coleman MP, Peake MD, Butler J, Young N, Bergstrom S, Hanna L, Jakobsen E, Kolbeck K, Sundstrom S, Engholm G, Gavin A, Gjerstorff ML, Hatcher J, Johannesen TB, Linklater KM, McGahan CE, Steward J, Tracey E, Turner D, Richards MA, Rachet B; ICBP Module 1 Working Group. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax. 2013 Jun;68(6):551-64. doi: 10.1136/thoraxjnl-2012-202297. Epub 2013 Feb 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.