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

Phase 3

Recruiting

• Conditions: Hand and Foot Syndrome; Erythrodysesthesia Syndrome; HFS; Colorectal Cancer
• Interventions: Drug: Celecoxib 200mg; Drug: Capecitabine-based chemotherapy

• Registration Number: NCT05327751
• Lead Sponsor: Tanta University

Brief 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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2022-04
• Study Start: 2022-04-01
• Study First Submitted: 2022-04-01
• Study First Submitted QC: 2022-04-07
• Last Update Submitted: 2022-04-07
• Study First Posted: 2022-04-14
• Last Update Posted: 2022-04-14
• Primary Completion: 2024-04-01
• Study Completion: 2025-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Celecoxib arm	Capecitabine-based chemotherapy	This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) in addition to 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. The study duration will be the duration of the 6 cycles.
Celecoxib arm	Celecoxib 200mg	This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) in addition to 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. The study duration will be the duration of the 6 cycles.
Control arm	Capecitabine-based chemotherapy	This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks).

Primary Outcome Measures

Name	Time	Method
The change in HFS-specific QOL questionnaire (HFS-14).	After each cycle (each cycle is 21 days).	Assessment of patients' quality of life using HFS-specific QOL questionnaire (HFS-14) based on patients' symptoms.
The change in HFS grading.	After each cycle (each cycle is 21 days).	The change in hand and foot syndrome (HFS) grading according to common terminology criteria of adverse events (CTCAE) version 5.0.

Secondary Outcome Measures

Name	Time	Method
The change in serum levels of tumor necrosis factor alpha (TNF-α).	At basline and after the sixth cycle (each cycle is 21 days).	The change in serum levels of tumor necrosis factor alpha (TNF-α) as a inflammatory marker.
The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.	At basline and after the sixth cycle (each cycle is 21 days).	The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.
The change in serum levels of malondialdehyde (MDA).	At basline and after the sixth cycle (each cycle is 21 days).	The change in serum levels of malondialdehyde (MDA) as oxidative stress marker.

Trial Locations

Locations (1)

Faculty of Pharmacy-Tanta University; 🇪🇬 Tanta, Egypt