Clinical trial NCT06822959: Pharmacogenetics, Therapeutic Drug Monitoring (TDM) and Active Pharmacovigilance as Innovative Tools Aimed at the Optimisation/ Appropriateness of Drug Therapy
Official title: Pharmacogenetics, Therapeutic Drug Monitoring (TDM) and Active Pharmacovigilance as Innovative Tools Aimed at the Optimisation/ Appropriateness of Drug Therapy and the Minimisation of the Risks of ADRs in Clinical Practice: a Multidisciplinary Approach Exportable at National Level
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adverse Drug Reaction (ADR)
Lead sponsor: Direzione centrale salute, politiche sociali e disabilità
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento Oncologico - Aviano
name: IRCCS Burlo Garofolo
First posted: 2025-02-12
Enrollment: 450
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are candidates for therapy with: Abemaciclib, Palbociclib, Ribociclib, Letrozole, Tamoxifen, Olaparib, Infliximab, Cyclophosphamide, Methotrexate, Irinotecan, Capecitabine, 5-Fluorouracil, Noraparib, Adalimumab, Imatinib, Regorafenib, Lenvatinib, Sorafenib, Sunitinib, Rucaparib, 6-MP/ Azathioprine

Brief summary: The primary goal of this observational study is to evaluate the feasibility of implementing a multidisciplinary approach based on pharmacogenetics, TDM (Therapeutic Drug Monitoring) and MedReview into the clinical practice in order to optimize the appropriateness of drugs prescription and to minimise the risk of Adverse Drug Reactions (ADRs) in adult cancer patients and in pediatric patients affected by chronic inflammatory diseases. This approach of active pharmacovigilance will also allow a better definition of the causality assessment of ADRs through the direct implementation of data quality in the reporting forms. The study may therefore constitute an example of an approach for both the prevention of ADRs and the optimization of drug use, and for the integration of pharmacogenetics, TDM, and the MedReview data into the National Pharmacovigilance Reports for an improved and innovative evaluation of adverse events, aiming at the implementation of this approach in the regional context.

Detailed description: Primary aim of the study:

To implement the use of pharmacogenetics, TDM, and MedReview at the regional level supporting their utility through an observational approach to assess the effects of these innovative methods, already active in IRCCS, for the optimization of appropriate drug use and minimization of ADR risk in adult and pediatric oncology patients, as well as pediatric patients with chronic inflammatory diseases. Specifically, the aim is to evaluate the incidence of ADRs in patients treated based on pharmacogenetics, TDM, and MedReview compared to historical cases treated according to the standard of care before the implementation of the proposed innovative methodologies.

Secondary aims of the study:

1. To evaluate the "Causality Assessment" between ADR and drug based on the enhanced data quality deriving from the integration of pharmacogenetics, TDM and MedReview into the Pharmacovigilance report.
2. To propose the systematic integration of the results related to pharmacogenetics, TDM, and MedReview within the existing fields of the current ADR reporting form. This aims to develop a proposal for updating AIFA procedures related to the inclusion of this type of evidence-based information in the National Pharmacovigilance Network (RNF), with a potential update of the reporting form.

Eligibility criteria: Inclusion Criteria:

Patients who are candidates for therapy with:

* Abemaciclib,
* Palbociclib,
* Ribociclib,
* Letrozole,
* Tamoxifen,
* Olaparib,
* Niraparib,
* Rucaparib,
* Imatinib,
* Sunitinib,
* Sorafenib,
* Regorafenib,
* Lenvatinib,
* Irinotecan,
* Capecitabine,
* 5-Fluorouracil,
* Infliximab,
* Cyclophosphamide,
* Methotrexate,
* Adalimumab,
* 6-Mercaptopurine/Azathioprine

Primary outcomes:
measure: Patients treated with study drugs tested with pharmacogenetic and TDM analysis
timeFrame: Up to 2 years
measure: MedReview reports
timeFrame: Up to 2 years
measure: ADRs in patients treated on the basis of pharmacogenetics, TDM and MedReview
timeFrame: Up to 2 years
measure: Comparison of ADRs in patients treated on the basis of pharmacogenetics, TDM and MedReview and retrospective data
timeFrame: Up to 2 years
Secondary outcomes:
measure: Integration of pharmacogenetics, TDM and MedReview information in the existing tool for the evaluation of "Causality assessment" between ADR and specific drug
timeFrame: Up to 2 years
measure: Proposal for updating the pharmacovigilance reporting forms including Pharmacogenetics, TDM and MedReview information in the National Network of Pharmacovigilance
timeFrame: Up to 2 years
measure: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 v3
timeFrame: Up to 2 years
measure: Costs of ADRs management
timeFrame: Up to 2 years
measure: Concordance between plasmatic concentration measured with conventional methods and with new methods such as Dried Blood Spot (DBS)
timeFrame: Up to 2 years
measure: Correlation between pharmacogenetic profile and drug exposure (TDM)
timeFrame: Up to 2 years
measure: Correlation between ADRs, TDM and pharmacogenetics analyses
timeFrame: Up to 2 years
measure: Correlation between ADRs, TDM and pharmacogenetics analyses
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico di Aviano (CRO)
state: Pordenone
city: Trieste
country: Italy
facility: IRCCS materno infantile Burlo Garofolo di Trieste
Study officials:
affiliation: Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS
name: Erika Cecchin
role: PRINCIPAL_INVESTIGATOR
References: