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

NCT05327751 | Unknown Phase 3

• 1 other identifier: 42022
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Hand and Foot Syndrome; Erythrodysesthesia Syndrome; HFS; Colorectal Cancer

Keywords

capecitapine induced hand and foot syndrome; Hand and Foot Syndrome; Erythrodysesthesia Syndrome; HFS; capecitabine based chemotherapy; Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• 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).

• 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 Outcomes (3)

• 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 tumor necrosis factor alpha (TNF-α).

  At basline and after the sixth cycle (each cycle is 21 days).

• The change in serum levels of malondialdehyde (MDA).

  At basline and after the sixth cycle (each cycle is 21 days).

Study Arms (2)

Celecoxib arm

ACTIVE COMPARATOR

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; Drug: Capecitabine-based chemotherapy

Control arm

PLACEBO COMPARATOR

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

Drug: Capecitabine-based chemotherapy

Interventions

Celecoxib 200mg DRUG

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

Celecoxib arm

Capecitabine-based chemotherapy DRUG

Capecitabine-based chemotherapy

Celecoxib arm; Control arm

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Faculty of Pharmacy-Tanta University

Tanta, Egypt

RECRUITING

MeSH Terms

Conditions

Hand-Foot Syndrome; Colorectal Neoplasms

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; 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)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Ahmed Mohamed Kettana

CONTACT

+201009241434; ahmed150848@pharm.tanta.edu.eg

Tarek Mohamed Mostafa, Professor of clinical pharmacy

CONTACT

+201154594035; tarek.mostafa@pharm.tanta.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical pharmacist

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 14, 2022
• Study Start: April 1, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2025
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

EG (1)