Feasibility of a Clinical Trial Comparing the Use of Cetirizine to Replace Diphenhydramine in the Prevention of Reactions Related to Paclitaxel

Study Overview
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Brief Summary
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Explore the randomized, controlled, double-blind design targeted for the final clinical trial to assess the acceptability of interventions and clinical outcome measures and to provide data making it possible to estimate the parameters necessary for the preparation, modification or even abandonment of the final study.

Detailed Description
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Paclitaxel is known to cause 30 to 40% of infusion-related reactions when no premedication is administered. It is agreed that all patients should receive premedication with dexamethasone, an H1 antagonist, such as diphenhydramine, and an H2 antagonist before the administration of paclitaxel. There are several cases where undesirable effects (eg. drowsiness, dry mouth, motor impatience) have been reported following the administration of this conventional premedication. Diphenhydramine is often accused because of its pharmacological properties. A definitive, randomized, double-blind, non-inferiority study can assess whether cetirizine, a non-sedating H1 antagonist, can be used as an effective and safe alternative to diphenhydramine in the prevention of paclitaxel infusion-related reactions. In the current proposed feasibility study, patients will be followed for the first two doses of paclitaxel. The goal is to explore the randomized, controlled, double-blind design targeted for the final clinical trial to assess the acceptability of interventions and clinical outcome measures and to provide data making it possible to estimate the parameters necessary for the preparation, modification or even abandonment of the final study.

Official Title
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Feasibility of a Randomized Controlled Clinical Trial Comparing the Use of Cetirizine to Replace Diphenhydramine in the Prevention of Reactions Related to Paclitaxel

Conditions
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Breast Cancer, Lung Cancer, Ovarian Cancer, Oesophageal Cancer, Head Cancer Neck, Cervical Cancer, Endometrial Cancer

Intervention / Treatment
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* Drug: Diphenhydramine
* Drug: Cetirizine
* Drug: Lactose pill
* Drug: Sodium chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Receiving intravenous chemotherapy treatments at the Maisonneuve-Rosemont hospital outpatient oncology clinic Starting their first lifetime treatment with paclitaxel (alone or in combination with other anticancer agents). Capable of giving free and informed consent and who agrees to participate by signing the consent form Aged 18 and over Able to complete questionnaires Exclusion Criteria: Does not understand French or English Taking chronic H1 antagonist orally Taking chronic systemic corticosteroids Contraindication or possible medical danger, such as a documented allergy or previous intolerance, related to the administration of cetirizine, diphenhydramine, placebo or any ingredient in their formulation Has received paclitaxel, docetaxel or paclitaxel nanoparticles linked to albumin in the past Receiving paclitaxel nanoparticles linked to albumin Severe renal impairment (Cockcroft-Gault <10 milliliters/minute) Pregnant or breastfeeding women Receiving paclitaxel under desensitization protocol Documented or reported dysphagia or other pathophysiological condition preventing a tablet from being swallowed whole Interactions preventing the full dose of oral cetirizine from being absorbed Participating in another clinical trial simultaneously

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Diphenhydramine + placebo<br>Diphenhydramine 50 mg intravenous given in a 50 milliliters bag of sodium chloride 0.9 percent, with famotidine, 30 minutes before the paclitaxel infusion. 15 minutes infusion. Lactose tablet 100 mg per os given 30 minutes before the paclitaxel infusion.with a 180 milliliters glass of water. | Drug: Diphenhydramine<br>* Drug identification number : 02369567<br>* Other names: Benadryl;Drug: Lactose pill<br>* Natural product number : 00501190<br>|
| Experimental: Cetirizine + placebo<br>Cetirizine tablet 10 mg per os given 30 minutes before the paclitaxel infusion.with a 180 milliliters glass of water. 1 milliliter of sodium chloride 0,9 percent intravenous given in a 50 milliliters bag of sodium chloride 0.9 percent, with famotidine, 30 minutes before the paclitaxel infusion. 15 minutes infusion. | Drug: Cetirizine<br>* Drug identification number : 02231603<br>* Other names: Reactine;Drug: Sodium chloride 0.9%<br>* Drug identification number : 00037796<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of drowsiness on Stanford Sleepiness Scale 1 hour after the administration of diphenhydramine | For treatment 1 and treatment 2 | 15 minutes before the administration of diphenhydramine. 1 hour after the administration of diphenhydramine. | 
| Change from baseline of drowsiness on Stanford Sleepiness Scale upon arrival at home | For treatment 1 and treatment 2 | 15 minutes before the administration of diphenhydramine. Upon arrival at home. | 
| Change from baseline of drowsiness on Stanford Sleepiness Scale the morning after the administration of diphenhydramine | For treatment 1 and treatment 2 | 15 minutes before the administration of diphenhydramine. Morning of day 2. | 
| Recruitment rate accomplished to recruit 24 participants for which a first dose of paclitaxel was administered between February and September 2020. | Number of participants per month recruited for which a first dose of paclitaxel was administered | Through study completion, 8 months | 
| Percentage of participants recruited, randomized and having received the first treatment of paclitaxel planned in the study between February and September 2020 following an assessment of their eligibility. | Number of participants recruited, randomized and having received the first treatment of paclitaxel planned in the study divided by the number of participants eligible to participate in the study | Through study completion, 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants per group who required stopping the infusion and/or using rescue medication. | Stopping the infusion and using rescue medication defined by the medical choice of the attending physician. For treatment 1 and treatment 2. | Day 1 | 
| Infusion-related reactions grade according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification | Grades will be determined using nurses notes. For treatment 1 and treatment 2 | Day 1 |