Evaluation of Hypersensitivity Reactions in Solid Tumor Patients Undergoing Paclitaxel Chemotherapy with and without Dexamethasone Premedication

The primary objective of this study is to evaluate the incidence of clinically relevant **hypersensitivity reactions** (HSRs) of grade ≥3, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, during paclitaxel-based chemotherapy. This evaluation compares a standard of care premedication regimen that includes **dexamethasone** with an experimental regimen that omits dexamethasone. The clinical relevance of this objective lies in its potential to inform safer and more effective premedication strategies for patients undergoing chemotherapy for solid tumors, potentially reducing the risk of severe HSRs.

Secondary objectives include: - Determining the incidence and severity of HSRs of any grade during paclitaxel-based chemotherapy with the standard premedication regimen compared to the experimental regimen. - Assessing the number of paclitaxel administrations and cumulative dose until the first occurrence of an HSR of any grade. - Evaluating the effect of dexamethasone omission on the patient's quality of life. - Determining the incidence and severity of adverse events related to dexamethasone. - Assessing the cost-effectiveness of the premedication regimens with and without dexamethasone from both healthcare and societal perspectives.

The clinical trial involves participants diagnosed with **solid tumors** who are scheduled to undergo paclitaxel-based chemotherapy. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a mastery of the Dutch language and must be able and willing to provide written informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that individuals are suitable for the study's primary objective, which is to evaluate the incidence of clinically relevant hypersensitivity reactions during chemotherapy. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the incidence of clinically relevant hypersensitivity reactions (HSRs) during paclitaxel-based chemotherapy with a standard premedication regimen including **dexamethasone** compared to an experimental regimen without it. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence recruitment on February 1, 2024, and conclude by January 1, 2027, with an estimated duration of three years.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (≥18 years), diagnosis of a solid tumor, and planned treatment with paclitaxel-based chemotherapy. The inclusion visit will also involve obtaining written informed consent. Follow-up visits will be scheduled to monitor the incidence and severity of HSRs, as well as any adverse events related to dexamethasone, using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The end-of-study visit will assess the primary and secondary endpoints, including the percentage of patients experiencing clinically relevant HSRs and the overall quality of life using validated questionnaires.

Participant involvement is expected to last for the duration of their chemotherapy treatment, with a maximum treatment period of five days for dexamethasone administration. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or the occurrence of severe adverse events. The trial aims to provide comprehensive data on the safety and efficacy of omitting dexamethasone from premedication regimens, potentially influencing future treatment protocols for patients with solid tumors undergoing chemotherapy.

The clinical trial involves the administration of two experimental medications, both containing **dexamethasone**, a corticosteroid used to reduce inflammation and suppress immune responses. The first medication is **Dexamethasone 4 mg tablets**, manufactured by Mercury Pharmaceuticals Ltd. This pharmaceutical form is a tablet, intended for **oral** administration. The dosage regimen allows for a maximum daily dose of 8 mg, with a total maximum dose of 40 mg over a treatment period of up to 5 days. The tablets are chemically synthesized and are not formulated for pediatric use.

The second experimental medication is **Dexamethasone Phosphate 4 mg/ml Solution for Injection**, produced by Pfizer Healthcare Ireland. This formulation is a **solution for injection**, designed for **intravenous** administration. The dosing schedule permits a maximum daily dose of 10 mg, with a cumulative maximum dose of 50 mg over a 5-day treatment period. Like the tablet form, this solution is chemically derived and is not intended for pediatric patients.

In this study, the experimental medications are compared against a standard-of-care premedication regimen that includes dexamethasone, to evaluate the incidence of clinically relevant hypersensitivity reactions (HSRs) during paclitaxel-based chemotherapy. The trial does not utilize a placebo or other comparator treatments. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by evaluating the incidence of clinically relevant **hypersensitivity reactions (HSRs)**, specifically those classified as grade ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint is the percentage of patients experiencing such HSRs during paclitaxel infusion, determined prospectively by oncology medical staff. Secondary endpoints include the incidence and severity of all grades of HSRs, the percentage of patients eligible for rechallenge with or without dexamethasone, the number of paclitaxel administrations and cumulative dose until the first HSR occurrence, and the incidence and severity of adverse events related to dexamethasone as measured by the Dexamethasone Symptom Questionnaire (DSQ)21.

Additional secondary endpoints involve assessing patient quality of life using the EuroQol-5 dimensions-5 levels (EQ-5D-5L) and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30). The total cost of treatment for both premedication regimens will also be evaluated from a healthcare and societal perspective. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial, ensuring a comprehensive assessment of the impact of omitting dexamethasone from premedication regimens during paclitaxel treatment.