Clinical trial NCT04237090: Feasibility of a Clinical Trial Comparing the Use of Cetirizine to Replace Diphenhydramine in the Prevention of Reactions Related to Paclitaxel
Official title: Feasibility of a Randomized Controlled Clinical Trial Comparing the Use of Cetirizine to Replace Diphenhydramine in the Prevention of Reactions Related to Paclitaxel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lung Cancer
Ovarian Cancer
Oesophageal Cancer
Head Cancer Neck
Cervical Cancer
Endometrial Cancer
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2020-01-22
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline of drowsiness on Stanford Sleepiness Scale 1 hour after the administration of diphenhydramine
timeFrame: 15 minutes before the administration of diphenhydramine. 1 hour after the administration of diphenhydramine.
measure: Change from baseline of drowsiness on Stanford Sleepiness Scale upon arrival at home
timeFrame: 15 minutes before the administration of diphenhydramine. Upon arrival at home.
measure: Change from baseline of drowsiness on Stanford Sleepiness Scale the morning after the administration of diphenhydramine
timeFrame: 15 minutes before the administration of diphenhydramine. Morning of day 2.
measure: Recruitment rate accomplished to recruit 24 participants for which a first dose of paclitaxel was administered between February and September 2020.
timeFrame: Through study completion, 8 months
measure: 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.
timeFrame: Through study completion, 8 months
Secondary outcomes:
measure: Proportion of participants per group who required stopping the infusion and/or using rescue medication.
timeFrame: Day 1
measure: Infusion-related reactions grade according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification
timeFrame: Day 1
Other outcomes:
measure: Proportion of participants who completed the study
timeFrame: Through the course of the study, 8 months
measure: Reasons of loss to follow-up using a home-made questionnaire
timeFrame: Day 1
measure: Maintenance of the blind in participants using a home-made questionnaire
timeFrame: Day 1
measure: Maintenance of the blind in nurses using a home-made questionnaire
timeFrame: Day 1
measure: Side effects experienced by participants using a home-made questionnaire
timeFrame: Day 2
Locations:
city: Montréal
country: Canada
facility: CIUSSS de l'Est-de-l'île-de-Montréal
state: Quebec
Study officials:
affiliation: Ciusss de L'Est de l'Île de Montréal
name: Matthieu Picard, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, Baker JR Jr, Van Echo DA, Von Hoff DD, Leyland-Jones B. Hypersensitivity reactions from taxol. J Clin Oncol. 1990 Jul;8(7):1263-8. doi: 10.1200/JCO.1990.8.7.1263.
citation: Picard M, Castells MC. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review. Clin Rev Allergy Immunol. 2015 Oct;49(2):177-91. doi: 10.1007/s12016-014-8416-0.
citation: Picard M. Management of Hypersensitivity Reactions to Taxanes. Immunol Allergy Clin North Am. 2017 Nov;37(4):679-693. doi: 10.1016/j.iac.2017.07.004. Epub 2017 Aug 18.
citation: Durham CG, Thotakura D, Sager L, Foster J, Herrington JD. Cetirizine versus diphenhydramine in the prevention of chemotherapy-related hypersensitivity reactions. J Oncol Pharm Pract. 2019 Sep;25(6):1396-1401. doi: 10.1177/1078155218811505. Epub 2018 Nov 12.
citation: Siderov J, Wendel N, Davis ID. Non-Sedating Antihistamines for Premedication in Ambulatory Oncology Patients. Journal of Pharmacy Practice and Research 2002; 32(2): 108-9.
citation: del Cuvillo A, Mullol J, Bartra J, Davila I, Jauregui I, Montoro J, Sastre J, Valero AL. Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol. 2006;16 Suppl 1:3-12. No abstract available.
citation: Banerji A, Long AA, Camargo CA Jr. Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review. Allergy Asthma Proc. 2007 Jul-Aug;28(4):418-26. doi: 10.2500/aap.2007.28.3015.
citation: Berger MJ, Vargo C, Vincent M, Shaver K, Phillips G, Layman R, Macrae E, Mrozek E, Ramaswamy B, Wesolowski R, Shapiro CL, Lustberg MB. Stopping paclitaxel premedication after two doses in patients not experiencing a previous infusion hypersensitivity reaction. Support Care Cancer. 2015 Jul;23(7):2019-24. doi: 10.1007/s00520-014-2556-x. Epub 2014 Dec 18.
citation: Beaucage-Charron J, Gaudet L, Lamothe S, Pelletier C, Pepin AS, Roy V, Charpentier F, Lordkipanidze M, Projean D, Bouchard P, Picard M. A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study. Support Care Cancer. 2022 Apr;30(4):3389-3399. doi: 10.1007/s00520-021-06734-4. Epub 2022 Jan 8.