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

Breast Cancer Clinical Trial

— PREMED-F1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04237090
• Other study ID #: 2020-2110
• Status: Completed
• Phase: Phase 3
• Start date: February 14, 2020
• Est. completion date: September 4, 2020

Study information

• Verified date: October 2020
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 4, 2020
• Est. primary completion date: August 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Head and Neck Neoplasms
• Head Cancer Neck
• Lung Cancer
• Oesophageal Cancer
• Ovarian Cancer

Intervention

Drug:
• Diphenhydramine
Drug identification number : 02369567
• Cetirizine
Drug identification number : 02231603
• Lactose pill
Natural product number : 00501190
• Sodium chloride 0.9%
Drug identification number : 00037796

Locations

Country	Name	City	State
Canada	CIUSSS de l'Est-de-l'île-de-Montréal	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal

Country where clinical trial is conducted

Canada, 

References & Publications (8)

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. Review. — View 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. — View Citation

del Cuvillo A, Mullol J, Bartra J, Dávila I, Jáuregui I, Montoro J, Sastre J, Valero AL. Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol. 2006;16 Suppl 1:3-12. Review. — View 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. — View 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. Review. — View 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. Review. — View 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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of participants who completed the study	Number of participants who will have completed the study in each group divided by the number of participants recruited in each group	Through the course of the study, 8 months
Other	Reasons of loss to follow-up using a home-made questionnaire	For treatment 1 and treatment 2	Day 1
Other	Maintenance of the blind in participants using a home-made questionnaire	At the end of paclitaxel infusion of treatment 2	Day 1
Other	Maintenance of the blind in nurses using a home-made questionnaire	At the end of paclitaxel infusion of treatment 1 and 2	Day 1
Other	Side effects experienced by participants using a home-made questionnaire	Focus on drowsiness, dry mouth, eyes or nose, dizziness and restlessness/excitement. For treatment 1 and treatment 2.	Day 2
Primary	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.
Primary	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.
Primary	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.
Primary	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
Primary	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	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
Secondary	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