Effect of Losartan on the Incidence and Severity of Chemotherapy-Induced Mucositis in Gastrointestinal Cancer Patients

NCT05871333 | Unknown Phase 2

• 1 other identifier: Losartan, Mucositis
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Mucositis is a common and clinically significant side effect of both anticancer chemotherapy and radiation therapy that can affect any portion of the gastrointestinal tract. Not only associated with an adverse symptom profile, but also it may limit patients' ability to tolerate treatment if not adequately prevented and managed. Moreover, it may be associated with secondary local and systemic infection and poor health outcomes, and generates additional use of healthcare resources resulting in additional costs. Based on study of 38 patients of mean age sixty-one years old diagnosed with colorectal carcinoma were included to evaluate gastrointestinal adverse effect with different schedules of FOLFOX. Incidence of oral mucositis with FOLFOX-4 Is 76%, FOLFOX-6 is 62%, mFOLFOX-6 is 79% and FOLFOX-7 is 93% Chemotherapy-induced mucositis is commonly described as a five-phase sequence: initiation (0-2 days),upregulation and activation of messengers (2-3 days), signal amplification (2-5 days), ulceration with inflammation (5-14 days) and healing (14-21 days) According to the model introduced by some studies the primary inducer involved in unleashing mucosal injury upon chemotherapy is the production of reactive oxygen species (ROS), leading to tissue inflammation and mucositis induction. Inflammatory signaling pathways are upregulated during high reactive oxygen species states which further contribute to cytotoxicity. leading to the third step in the oral mucositis pathway. In this inflammatory phase, cytokines including Tissue Necrosis Factor alpha (TNF-α), prostaglandins, Nuclear factor Kappa β (NF-кβ), and interleukin (IL) 1β are released. The cytotoxic effects of chemotherapy, inflammation, and reactive oxygen species-mediated DNA damage result in gradual apoptosis of mucosal epithelial cells. Ulcerative sites become relatively neutropenic which predisposes them to bacterial and yeast infections. These bacterial toxins further simulate the underlying inflammatory state through release of additional cytokines. It is necessary to emphasize that oral mucositis is frequently documented only in its advanced phases owing to the requirements for clinical therapy and assistance. Therefore, the search for new active ingredients that could be used in the prevention (and even treatment) of oral and intestinal mucositis is of utmost importance.

Conditions

Chemotherapy; Colorectal Cancer; Intestinal Mucositis; Oral Mucositis

Keywords

Losartan; Colorectal Cancer; Chemotherapy-Induced Mucositis

Outcome Measures

Primary Outcomes (3)

• Change in Occurrence of oral mucositis

  Assessment the occurrence of oral mucositis by physical examination of oral cavity

  monthly for 6 months

• change in Severtity of Oral Mucositis

  Assessment of the severity of oral mucositis using the national cancer institute common

  monthly for 6 months

• change in severity of intestinal mucositis

  assessment of the severity of oral mucositis using the national cancer institute terminology criteria version 5.0

  monthly for 6 months

Secondary Outcomes (4)

• Evaluation of cancer control by Ultrasound

  at Baseline and at week 24 ( end of study)

• Quality of life questionnaire

  monthy for 6 months

• Laboratory evaluation of TNF-α level

  baseline and at week 16

• Laboratory evaluation of Interleukin-1β level

  Baseline and at week 16

Study Arms (2)

Standard of care

NO INTERVENTION

Patients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state.

standard of care + Losartan

EXPERIMENTAL

Patients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/ m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state. In addition to Losartan 50 mg/day orally for 4 months.

Drug: Losartan 50mg Tab

Interventions

Losartan 50mg Tab DRUG

Losartan 50 mg oral tablets

Also known as: Angiotension receptor blockers

standard of care + Losartan

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged 18 years old or more.
• Patients diagnosed with gastrointestinal cancer eligible for chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance ≤ 2.
• Platelet count more than 100 × 10\^9/L.
• Absolute neutrophil count: greater than 1.5 × 10\^9/L.
• Aspartate aminotransferase level up to 2.5 times the upper limit normal.
• Serum bilirubin level not more than 1.5 times the institutional upper limit normal.
• Serum creatinine levels up to 1.5 mg% and 1.4 mg% for males and females respectively.

You may not qualify if:

• Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
• Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema.
• Pregnant or breastfeeding women.
• Females in child bearing age not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception.
• Patient reported history or electronic medical record history of kidney disease, defined as:
• Any history of dialysis. History of chronic kidney disease stage IV. Estimated Glomerular Filtration Rate (eGFR) of \< 30ml/min/1.73 m2 Other Kidney disease that in the opinion of investigator, would affect Losartan Clearance.
• Patient reported dehydration and significantly decreased urine output in the past 72 hours.
• Most recent systolic blood pressure prior to enrollment \<110 mmHg.
• Current participation in any other clinical investigation.
• Currently taking any drug contraindicated with Losartan administration.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Hospital

Cairo, Egypt

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Stomatitis

Interventions

Losartan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Amira Y mohamed

  Ain Shams University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amira Y Mohamed

CONTACT

01020435341; amira.yousry@pharma.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Model Details: Group I: Patients will receive only their standard therapy for 4 months. Group II: will receive the studied drug orally in addition to their standard therapy

Study Record Dates

• First Submitted: March 15, 2023
• First Posted: May 23, 2023
• Study Start: July 17, 2023
• Primary Completion: June 1, 2024
• Study Completion: July 1, 2024
• Last Updated: July 19, 2023

Record last verified: 2023-07

Locations

EG (1)