Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer

Colorectal Cancer Clinical Trial

— HFS  

Official title:

Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327751
• Other study ID #: 42022
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2022
• Source: Tanta University
• Contact: Ahmed Mohamed Kettana
• Phone: +201009241434
• Email: ahmed150848[@]pharm.tanta.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of malignancy-related mortality. Capecitabine has been approved for the treatment of colorectal cancer as first-line therapy. About 50%-68% of patients who take capecitabine develop Hand-foot syndrome. Hand-foot syndrome (HFS) is the most common adverse event of capecitabine-based chemotherapy. Initial symptoms of HFS are dysesthesia, tingling in the palms, fingers, and soles of the feet, and erythema, which may progress to an extremely painful and debilitating condition without prompt management. These symptoms can potentially lead to a worsened quality of life in patients taking capecitabine-based chemotherapy. Moreover, the adverse reaction necessitates dose-reduction or withdrawal of the chemotherapeutic agent. The mechanisms of HFS are still unknown, and there are limited data available on how to prevent them or manage them. However, different hypotheses of capecitabine-induced HFS pathogenesis have been suggested. One of the hypotheses stated that HFS is a kind of inflammation mediated by cyclooxygenase's (COX-2) over expression in palm and feet by capecitabine and its metabolites causing elevation of inflammatory markers as tumor necrosis factor alpha (TNF-α). COX-2 enzyme plays a main role in inflammation and pain. Therefore, celecoxib which is selective (COX-2) inhibitor may have a key role in the HFS treatment plan. A retrospective study and two prospective studies showed that combining capecitabine with celecoxib, a selective COX-2 inhibitor, can significantly reduce capecitabine-related HFS in colorectal cancer patients. Those studies were dependent on HFS grading only without measuring any markers. So, in our study we assess possible protective effect of celecoxib against capecitabine induced HFS and measure inflammatory marker as tumor necrosis factor alpha (TNF-α), oxidative stress marker as Malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) enzyme to show whether capecitabine induced HFS is caused by COX-2 mediated inflammation or not.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

• Age: 18-65 years old.
• Gender: Male and female.
• Newly diagnosed colorectal cancer patients who are scheduled to receive capecitabine-based chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status < 2
• Patients with adequate renal function (Sr. creatinine < 1.2 mg/dl or eGFR = 90 ml/min).
• Patients with adequate hepatic function (Sr. bilirubin < 1.2 mg/dl).

Exclusion criteria:

• Pregnant and lactating females.
• Patients with cardiovascular disease (congestive heart failure, cardiac arrhythmia, or coronary artery disease, …. etc.).
• History of H-Pylori infection.
• Patients with a known hypersensitivity to any of the used drugs.
• Patients with any contraindication to any of the used drugs.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Hand and Foot Syndrome
• Hand-Foot Syndrome
• Syndrome

Intervention

Drug:
• Celecoxib 200mg
200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle.
• Capecitabine-based chemotherapy
Capecitabine-based chemotherapy

Locations

Country	Name	City	State
Egypt	Faculty of Pharmacy-Tanta University	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in HFS grading.	The change in hand and foot syndrome (HFS) grading according to common terminology criteria of adverse events (CTCAE) version 5.0.	After each cycle (each cycle is 21 days).
Primary	The change in HFS-specific QOL questionnaire (HFS-14).	Assessment of patients' quality of life using HFS-specific QOL questionnaire (HFS-14) based on patients' symptoms.	After each cycle (each cycle is 21 days).
Secondary	The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.	The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.	At basline and after the sixth cycle (each cycle is 21 days).
Secondary	The change in serum levels of tumor necrosis factor alpha (TNF-a).	The change in serum levels of tumor necrosis factor alpha (TNF-a) as a inflammatory marker.	At basline and after the sixth cycle (each cycle is 21 days).
Secondary	The change in serum levels of malondialdehyde (MDA).	The change in serum levels of malondialdehyde (MDA) as oxidative stress marker.	At basline and after the sixth cycle (each cycle is 21 days).