Cancer
Conditions
Brief summary
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
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.
Interventions
OTHERBlood 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
Sponsors
Agence Nationale de sécurité du Médicament
Institut Bergonié
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Severe Toxicity | During treatment, up to 12 months or within 4 weeks following definitive treatment discontinuation, an average of 5 months. | 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). |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 41 |
| 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). | 171 |
| 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). | 99 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Only patient treated by TKI without anti-angiogenic action. He was excluded due to selection bias. | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Retrospective Cohort A | Retrospective Cohort B | Total | Prospective Cohort |
|---|---|---|---|---|
| Age, Continuous | 74 years | 76 years | 75 years | 79 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment France | 171 Participants | 99 Participants | 311 Participants | 41 Participants |
| Sex: Female, Male Female | 98 Participants | 36 Participants | 150 Participants | 16 Participants |
| Sex: Female, Male Male | 73 Participants | 63 Participants | 161 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 41 | 62 / 171 | 46 / 99 |
| other Total, other adverse events | 36 / 41 | 131 / 171 | 76 / 99 |
| serious Total, serious adverse events | 14 / 41 | 75 / 171 | 43 / 99 |
Outcome results
Primary
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).
Time frame: During treatment, up to 12 months or within 4 weeks following definitive treatment discontinuation, an average of 5 months.
Population: Eligible and assessable population : All eligible patients who have received at least one TKI administration were included in analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prospective Cohort | Rate of Severe Toxicity | 14 Participants |
| Retrospective Cohort A | Rate of Severe Toxicity | 75 Participants |
| Retrospective Cohort B | Rate of Severe Toxicity | 43 Participants |