Predicting Severe Toxicity of Targeted Therapies in Elderly Patients With Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Predicting Severe Toxicity of Targeted Therapies in Elderly Patients With Cancer

Conditions
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Cancer

Intervention / Treatment
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* Other: Blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective cohort<br>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<br>* 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<br>|
| Retrospective cohort A<br>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<br>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?
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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. |