Predicting Severe Toxicity of Targeted Therapies in Elderly Patients With Cancer (PreToxE)

In order to assess the important issue of the safety of antiangiogenic TKI in geriatric population we set up this project which aims to identify, among clinical, biological, pharmacokinetic data, predictive factors for severe toxicity of antiangiogenic TKI (sunitinib, sorafenib, pazopanib, regorafenib, axitinib) in patients over 70 year-old.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Other: Blood sample

Detailed Description

This is a prospective cohort with collection of biological samples, including 300 patients > 70 year-old treated in multicenter with antiangiogenic TKI regularly approved for metastatic cancers. Data on clinical and biological characteristics of the patient, disease and treatment as well as pharmacogenomics will be centrally collected at the beginning of the treatment. Drug exposure-safety analyses will be performed through assessment of drug through levels (Cmin). Primary endpoint is severe toxicity defined as treatment-related death, hospitalization or disruption of treatment for more than three weeks.

• Study Type: Observational
• Enrollment (Actual): 312

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lyon Cedex 08, France, 69373
    • Centre Leon Berard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients without major violations of the eligibility criteria are included in the eligible population. In case of violation of the eligibility criteria, the steering committee will assess for each patient, whether the violation is minor or major.

All eligible patients who have received at least one TKI administration were included in analysis.

Description

Inclusion Criteria:

• Age ≥ 70 years
• Treatment with pazopanib, regorafenib, sorafenib, sunitinib,axitinib in the context of market authorization
• Voluntary signed and dated written informed consent prior to any study specific procedure.

Exclusion Criteria:

• Patient treated in a context of clinical trial
• Patient with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective cohort; Prospective cohort involving patients treated in four distinct centers. Patients were treated with a tyrosine kinase inhibitor (TKI) prescribed as part of a marketing authorization (MA). All patients without major violations of the eligibility criteria are included in the eligible population. In case of violation of the eligibility criteria, the steering committee will assess for each patient, whether the violation is minor or major. All eligible patients who have received at least one TKI administration were included in analysis.	Other: Blood sample; One blood sample before treatment initiation (Cycle 1 Day predose) for pharmacogenomics One blood sample at the end of the firth month of treatment (postdose) for pharmacokinetic
Retrospective cohort A; Retrospective cohort of patients treated at the Institut Bergonié (Bordeaux, France). Patients were treated with a tyrosine kinase inhibitor (TKI) prescribed as part of a marketing authorization (MA). All patients without major violations of the eligibility criteria are included in the eligible population. In case of violation of the eligibility criteria, the steering committee will assess for each patient, whether the violation is minor or major. All eligible patients who have received at least one TKI administration were included in analysis.
Retrospective cohort B; Retrospective cohort of patients treated at the Centre Antoine Lacassagne(Nice, France). Patients were treated with a tyrosine kinase inhibitor (TKI) prescribed as part of a marketing authorization (MA). All patients without major violations of the eligibility criteria are included in the eligible population. In case of violation of the eligibility criteria, the steering committee will assess for each patient, whether the violation is minor or major. All eligible patients who have received at least one TKI administration were included in analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Severe Toxicity	Severe toxicity was defined as any TKI-related adverse events (AE) leading to any one of the following events: death, persistent or significant disability/incapacity (defined as a permanent physical or mental impairmentwhich seriously limits one or more functional capacities such as mobility, communication, self-care, self-direction, or interpersonal skills), unexpected hospitalization, drug discontinuation for more than three weeks or definitive discontinuation. All adverse events (AE) were graded as per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.0).	During treatment, up to 12 months or within 4 weeks following definitive treatment discontinuation, an average of 5 months.

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Collaborators: Agence Nationale de sécurité du Médicament

Publications and helpful links

General Publications

• Lebreton C, Cantarel C, Toulza E, Desgrippes R, Bozec L, Saada E, Ducoulombier A, Tardy M, Paillaud E, Lalet C, Bellera C, Italiano A. Incidence and prognostic factors of clinically meaningful toxicities of kinase inhibitors in older patients with cancer: The PreToxE study. J Geriatr Oncol. 2021 May;12(4):668-671. doi: 10.1016/j.jgo.2020.09.020. Epub 2020 Sep 23.

Helpful Links

• Journal of Geriatric Oncology

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2016
• Primary Completion (Actual): November 19, 2019
• Study Completion (Actual): November 19, 2019

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 26, 2016

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: IB 2015-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No