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

NCT05852990 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CEI/1565/21 INCAN/CEI/0074/22
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer With EGFR Mutation

Keywords

Non-Small Cell Lung Cancer; EGFR mutation; Glutamine; Lactobacillus reuteri; standard-care diet

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Grade of gastrointestinal toxicity

  Every two weeks, from first dose of TKI therapy up to six weeks.

• Measurement of health related quality of life (QoL)

  Every two weeks, from first dose of TKI therapy up to six weeks.

• Measurement of quality of life (QoL) for lung cancer patients

  Every two weeks, from first dose of TKI therapy up to six weeks.

Study Arms (2)

Intervention diet

EXPERIMENTAL

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

Standard diet

NO INTERVENTION

Astringent diet from baseline treatment up to 6 weeks or death.

Interventions

Glutamine plus L. reuteri COMBINATION_PRODUCT

Glutamine plus Lactobacillus reueri twice daily for up to 6 weeks or death

Also known as: Glutapak-R

Intervention diet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Nacional de Cancerologia de Mexico: lead

Study Sites (1)

Instituto Nacional de Cancerologia de Mexico

Mexico City, Mexico City, 14080, Mexico

RECRUITING

Related Publications (7)

• 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.

  PMID: 22387006 BACKGROUND

• 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.

  PMID: 21565398 BACKGROUND

• 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.

  PMID: 23399908 BACKGROUND

• 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.

  PMID: 32493068 BACKGROUND

• 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.

  PMID: 27749689 BACKGROUND

• 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.

  PMID: 22489794 BACKGROUND

• 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.

  PMID: 20170547 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Glutamine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Study Officials

• Oscar G Arrieta Rodriguez, M.D., M.Sc.

  Instituto Nacional de Cancerología de México

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oscar G Arrieta Rodriguez, M.D., M.Sc.

CONTACT

556280400; ogar@unam.mx

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Thoracic Oncology Unit and Personalized Medicine Laboratory

Model Details: Patients with Non-Small Cell Lung Cancer and EGFR Mutation receiving first or second generation-TKI therapy.

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: May 10, 2023
• Study Start: March 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 12, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

ME (1)