Effect of Atorvastatin on 5-Fluorouracil Induced Mucositis

NCT04151355 | Unknown

• 1 other identifier: 216
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

5-Fuorouracil (5-Fu) remains one of the most effective and most commonly used drugs to treat colorectal cancer. Mucositis is a major complication that occurs in approximately 80% of patients receiving 5-FU and results in abdominal bloating as well as vomiting and diarrhea. oral mucositis (OM) are often very painful and compromise nutrition and oral hygiene as well as increase risk for local and systemic infection. OM is characterized by an intense inflammatory reaction on the mucosa lamina propria cells, which results in activation of the transcription factor NF-kB. The activation of NF-kB leads to transcription of genes involved in the synthesis of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Agents known to attenuate the expression of cytokines have demonstrated efficacy in the prevention of experimental mucositis. The use of atorvastatin were associated with reduced production of TNF-α and IL-1β and decreased neutrophil infiltration evidenced by histopathological analysis and Myeloperoxidase (MPO) activity. In addition, atorvastatin also reduced oxidative stress and induced an increase in non-protein sulfhydryl groups showing anti-inflammatory and immunomodulatory action.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• incidence of mucositis

  screening the patients seeking mucositis \& grading mucositis using Common Terminology Criteria for Adverse Events, CTCAE version 5 ( ranging from grade 1 of better outcome to 5 of worst outcome ) and evaluating the effect of atorvastatin on mucositis

  6 months

Secondary Outcomes (5)

• grade of mucositis

  6 month

• Pain score

  6 month

• Effect of mucositis on patient's daily life

  6-months

• liver function test

  6 months

• serum levels of tumor necrosis factor α (TNF-α)

  6 months

Study Arms (2)

Atorvastatin group

EXPERIMENTAL

50 colorectal cancer patients receiving FOLFOX 6: (Oxaliplatin 85mg/m2 IV over 2 hrs + leucovorin 400mg/m2 IV over 2 hrs, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks) in addittion to atorvastatin (20 mg once daily) or FOLFIRI 6:( Irinotecan 180mg/m2 IV + leucovorin 400mg/m2 IV, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks) in addittion to atorvastatin (20 mg once daily) in addittion to atorvastatin (20 mg once daily)

Drug: Atorvastatin 20mg

Control group

NO INTERVENTION

50 colorectal cancer patients receiving FOLFOX 6: (Oxaliplatin 85mg/m2 IV over 2 hrs + leucovorin 400mg/m2 IV over 2 hrs, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks) or FOLFIRI 6:( Irinotecan 180mg/m2 IV + leucovorin 400mg/m2 IV, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks)

Interventions

Atorvastatin 20mg DRUG

atorvastatin (20 mg once daily)

Atorvastatin group

Eligibility Criteria

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

You may qualify if:

• Adult patients (\>18 years old).
• Colon cancer patients ???? who will receive adjuvant FOLFOX 6\& FOLFIRI 6 for 6 cycles.
• ECOG performance status 0-2
• Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count ≥100,000/mm3), liver function (serum total bilirubin \<1.5 mg/dl), renal function (creatinine \<1.5 mg/dl).

You may not qualify if:

• Patients who have Clinical GIT mucositis or Periodontal disease.
• Patients with other primary malignancy.
• Patients receiving mTOR inhibitors (eg, rapamycin, everolimus, and temsirolimus), EGFR inhibitors (eg, bevacizumab and erlotinib) and tyrosine-kinase inhibitors (eg, sorafenib and sunitinib).
• Hypersensitivity to Atorvastatin.
• Pregnant and lactating women. 7- Patients treated with ATV for any other indication. 8- Patient who already have a mucositis

Sponsors & Collaborators

• Ain Shams University: lead
• Nasser Institute For Research and Treatment: collaborator

Study Sites (1)

Faculty of Pharmacy

Cairo, Egypt

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Atorvastatin

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Radwa S. Gad, diplome

  clinical pharmacist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rasha M. Elsayed AbdelMotagalee, Consultant

CONTACT

01224122560; elsayedonco@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist at nasser institute

Model Details: Prospective, Randomized, controlled, open-label pilot study will be conducted on 100 colon cancer patients receiving 5-FU adjuvant FOLFOX -6 \& FOLFIRI-6 therapy.

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 5, 2019
• Study Start: October 1, 2019
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: November 5, 2019

Record last verified: 2019-11

Locations

EG (1)