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

Sponsor

Tanta University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05327751

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hand and Foot Syndrome Erythrodysesthesia Syndrome HFS Colorectal Cancer	Drug: Celecoxib 200mg Drug: Capecitabine-based chemotherapy	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Celecoxib arm 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.	Drug: Celecoxib 200mg 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. Drug: Capecitabine-based chemotherapy Capecitabine-based chemotherapy
Placebo Comparator: Control arm This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks).	Drug: Capecitabine-based chemotherapy Capecitabine-based chemotherapy

Arm

Intervention/Treatment

Active Comparator: Celecoxib arm

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.

Drug: Celecoxib 200mg

200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle.

Drug: Capecitabine-based chemotherapy

Capecitabine-based chemotherapy

Placebo Comparator: Control arm

This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks).

Drug: Capecitabine-based chemotherapy

Capecitabine-based chemotherapy

Outcome Measures

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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 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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.