The Possible Protective Role of Ketotifen Against Oxaliplatin Induced Peripheral Neuropathy

NCT ID: NCT05624138

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-09
• Study Completion Date: 2025-06-30

Brief 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.

Detailed Description

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.

• Study design

This study will be a Randomized placebo controlled parallel study. Sixty four patients with stage III colorectal cancer will be scheduled to receive 12 cycles of modified FOLFOX-6 (folinic acid, flurouracil and oxaliplatin). Patients will be recruited from the Oncology Department, Tanta University Hospital, Tanta, Egypt. Staging will be done according to the American Joint Committee on Cancer 7th edition staging (Edge and Compton, 2010). At admission, patients will be randomized through sealed envelopes method with assignment codes (A and B) into two groups to receive either Placebo or ketotifen in addition to the chemotherapeutic regimen:

Group one (Placebo group or code A; n=32)

Patients will receive 12 cycles of modified FOLFOX-6 regiment plus placebo tablets daily throughout the twelve chemotherapy cycles. The chemotherapy cycles will be received every 2 weeks and will be as follows:

Day 1: Oxaliplatin 85 mg/m2 intravenous infusion in 250-500 mL 5% dextrose solution and leucovorin 400 mg/m2 intravenous infusion in 5% dextrose solution both were given over 120 minutes at the same time in separate bags using a Y-line access, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2-4 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenous infusion in 500 mL 5% dextrose solution as a 46-hour infusion.

Group two (Ketotifen group or code B; n=32) Patients will receive the same chemotherapy regimen as group one in addition to oral ketotifen 2 mg daily throughout the twelve chemotherapy cycles.

Intravenous 5-HT3 antagonist plus pantoprazole will be administered to all participants before each cycle as prophylactic therapy against chemotherapy induced nausea, vomiting and mucositis.

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.

Conditions

Neuropathy;Peripheral

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

placebo

Group I Placebo group n=32 Patients will receive 12 cycles of modified FOLFOX-6 regiment plus placebo tablets 2mg daily throughout the twelve chemotherapy cycles. The chemotherapy cycles will be received every 2 weeks and will be as follows:

Day 1 and Day 15: Oxaliplatin 85 mg/m2 intravenous infusion in 250-500 mL 5% dextrose solution and leucovorin 400 mg/m2 intravenous infusion in 5% dextrose solution both were given over 120 minutes at the same time in separate bags using a Y-line access, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2-4 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenous infusion in 500 mL 5% dextrose solution as a 46-hour infusion.

Group Type: PLACEBO_COMPARATOR

Placebo tablets

Intervention Type: DRUG

12 cycles of modified FOLFOX-6 regimen (Oxaliplatin, Fluorouracil, calcium leucovorin) with 2 mg placebo tablets

ketotifen oral tablets

Group II ketotifen group n=32 Patients will receive 12 cycles of modified FOLFOX-6 regiment plus ketotifen tablets 2mg daily throughout the twelve chemotherapy cycles. The chemotherapy cycles will be received every 2 weeks and will be as follows:

Day 1 and Day 15 : Oxaliplatin 85 mg/m2 intravenous infusion in 250-500 mL 5% dextrose solution and leucovorin 400 mg/m2 intravenous infusion in 5% dextrose solution both were given over 120 minutes at the same time in separate bags using a Y-line access, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2-4 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenous infusion in 500 mL 5% dextrose solution as a 46-hour infusion

Group Type: ACTIVE_COMPARATOR

Ketotifen Oral Tablet

Intervention Type: DRUG

ketotifen is a potent anti histaminic drug that may prevent oxaliplatin induced peripheral neuropathy and mucositis and will be administered 2 mg daily along with the 12 cycles of modified Folfox-6 regimen

Interventions

Placebo tablets

12 cycles of modified FOLFOX-6 regimen (Oxaliplatin, Fluorouracil, calcium leucovorin) with 2 mg placebo tablets

Intervention Type: DRUG

Ketotifen Oral Tablet

ketotifen is a potent anti histaminic drug that may prevent oxaliplatin induced peripheral neuropathy and mucositis and will be administered 2 mg daily along with the 12 cycles of modified Folfox-6 regimen

Intervention Type: DRUG

Other Intervention Names

Oxaliplatin, Fluorouracil, calcium leucovorin; ketotifen

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Salma Samah Sayed Wahby

clinical pharmacist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Oncology department Tanta university

Tanta, Other, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

salma S wahby, Master

Role: CONTACT

salmawahby135@outlook.com

00201111103067

Tarek M mostafa, Professor of clinical pharmacy

Role: CONTACT

tarek.mostafa@pharm.tanta.edu.eg

01154594035

Facility Contacts

salma S wahby

Role: primary

salmawahby135@outlook.com

01111103067

Other Identifiers

ketotifen in neuropathy

Identifier Type: -

Identifier Source: org_study_id