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

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

Overview

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.

Interventions

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

Primary outcome measures

• Diarrhea toxicity [Time frame: every two weeks, from first dose of TKI therapy up to six weeks.]
• Functional Assessment of Chronic Illness Therapy [Time frame: Every two weeks, from first dose of TKI therapy up to six weeks.]

Secondary outcome measures (3)

• Grade of gastrointestinal toxicity [Time frame: Every two weeks, from first dose of TKI therapy up to six weeks.]
• Measurement of health related quality of life (QoL) [Time frame: Every two weeks, from first dose of TKI therapy up to six weeks.]
• Measurement of quality of life (QoL) for lung cancer patients [Time frame: Every two weeks, from first dose of TKI therapy up to six weeks.]

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.

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

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Mexico · 1 center

• Instituto Nacional de Cancerologia de Mexico — Mexico City

Publications

• 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
• 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
• 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 popul PMID 23399908
• 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
• 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
• 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 PMID 22489794
• 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: 10.1186/14 PMID 20170547

Identifiers

NCT: NCT05852990 · CEI/1565/21 INCAN/CEI/0074/22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗