The Possible Protective Role of Ketotifen Against Oxaliplatin Induced Peripheral Neuropathy

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of current study is to evaluate the possible protective role of Ketotifen against oxaliplatin-induced peripheral sensory neuropathy in patient with stage III colorectal cancer.

This study will be a randomized placebo controlled parallel study.64 patients with colorectal cancer will be randomized to 2 groups:

Group I (control group; n=32) which will receive 12 cycles of modified FOLFOX-6 regimen plus placebo tablets twice daily.

Group II (ketotifen group; n=32) which will receive modified FOLFOX-6 regimen in addition to ketotifen 2 mg daily

Blood sample collection and biochemical assessment:

• Serum IL-6 as a marker of inflammation.

• Serum superoxide dismutase (SOD) as a biomarker of oxidative stress.

• Serum neurotensin as a biomarker for neuropathy.

Assessment of oxaliplatin induced peripheral sensory neuropathy will be done through:

• The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy at baseline and by the end of every two oxaliplatin cycles.

• The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group "FACT/GOG-Ntx-12" at baseline and by the end of every two oxaliplatin cycles.

• The assessment of the severity of neuropathic pain through brief pain inventory short form "BPI-SF" worst item. Severity of neuropathic pain will be assessed at baseline and by the end of every two oxaliplatin cycles.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tanta University
• Treatments: Fluorouracil; Ketotifen; Leucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Patients with histologically confirmed diagnosis of Stage III colorectal cancer.

• Patients who will be scheduled to receive modified FOLFOX-6.

• Patients with no contraindication to chemotherapy.

• Males and females aged ≥ 18 years old.

• Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).

• Patients with adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance (ClCr) ˃ 45 mL/min).

• Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).

• Patients with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG) score.

Exclusion Criteria:

• Children < 18 years old.

• Prior exposure to neurotoxic chemotherapy (Oxaliplatin, cisplatin, vincristine, paclitaxel, or docetaxel, INH) for at least 6 months prior the study treatment.

• Evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes, brain tumor, brain trauma).

• Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases, hepatitis C.

• History of known allergy to oxaliplatin or other platinum agents.

• Patients with other inflammatory or stressful conditions.

• Patients with glaucoma, cataract, other chronic eye disease, seizure, diabetes, heart diseases, low blood pressure, dizziness, vertigo, ménière's disease and CNS disorders.

• Concomitant use of multivitamins (vitamins E, C, A), tricyclic antidepressants, other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin, etc…).

• Patients on amifampridine, bupropion and donepezil.

• Concurrent active cancer originating from a primary site other than colon or rectum.

• Pregnant and breastfeeding women.