Ignite Creation Date:
2024-05-06 @ 3:29 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04659343
Status:
RECRUITING
Last Update Posted:
2024-02-05
First Post:
2020-11-20
Brief Title:
TDM for Optimized Outcome in Patients With mRCC
Sponsor:
Aarhus University Hospital
Organization:
University of Aarhus
Study Overview
Official Title:
Therapeutic Drug Monitoring for Optimized Outcome in Patients With Metastatic Renal Cell Carcinoma
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this observational study is to assess the role of plasma concentration monitoring of treatment drugs for patients with metastatic renal cell carcinoma mRCC in terms of efficacy and side effects
Furthermore the investigators examines the role of anti-drug antibodies and receptor polymorphisms in CTLA-4 and PD-1 receptors in treatment failure among patients with mRCC treated with check point immunotherapy Moreover polymorphisms in the UGT1A1 gene will be correlated with the pazopanib treatment dose
Furthermore the investigators examines the role of anti-drug antibodies and receptor polymorphisms in CTLA-4 and PD-1 receptors in treatment failure among patients with mRCC treated with check point immunotherapy Moreover polymorphisms in the UGT1A1 gene will be correlated with the pazopanib treatment dose
Detailed Description:
BACKGROUND
Treatment of metastatic renal cell carcinoma mRCC is ineffective among 25 of patients However treatment still reduces patients quality of life
From clinical experience interindividual dose requirements vary greatly among patients with mRCC treated with tyrosine kinase inhibitors
The investigators expect this to partly be explained by great variation in the plasma concentration of treatment drugs Furthermore treatment failure among patients with mRCC treated with check point immunotherapy has not been fully investigated
RATIONALE
The few studies concerning plasma concentration measurement of tyrosine kinase inhibitors in patients with mRCC have found that a certain level of drug concentration is necessary for treatment efficacy The role of plasma concentration in side effects is yet unknown
Anti drug antibodies against the check point inhibitor ipilimumab has been shown to reduce efficacy and lead to treatment failure among patients with malignant melanoma Receptor polymorphism in CTLA-4 and PD-1 receptors in terms of efficacy have not yet been studied
A therapeutic drug interval for TKI treatment will allow for quicker and more precise dosing and early signs of treatment failure of checkpoint immunotherapy will allow for quicker change of therapy or define a subgroup of patients who will not benefit from checkpoint immunotherapy and therefore should be offered another effective treatment instead
HYPOTHESIS
1 Patients treated with TKIs for more than 6 months have an optimal plasma trough concentration Objective response rate progression free survival PFS overall survival OS and toxicity in these patients are favorable compared with pivotal phase III study results
2 Patients treated with CPI obtaining response have a higher plasma trough concentration value of ipilimumab and nivolumab than patients with progressive disease PD Patients treated with CPI who develop PD have a higher amount of ADA than patients with response to treatment
3 Certain polymorphisms in CTLA-4 and PD-1 are associated with poor outcome
4 UGT1A1 polymorphism is associated with improved survival despite dose reductions in patients treated with pazopanib
MATERIALS AND METHODS
All eligible TKI-patients will have blood samples drawn at each clinical visit during a 6-months period
The plasma concentration of TKIs will be measured with liquid chromatography-mass spectrometry at the Department of Clinical Biochemistry at Aarhus University Hospital
All eligible CPI-patients will have blood samples drawn from start CPI-treatment and during treatment until treatment failure or full treatment 2 years
Analysis of checkpoint immunotherapy will be be done using in-house bead-based assays anti-human IgG detection antibody and in-house developed flow cytometry-based assay at the Institute for Inflammation Research at Rigshospitalet
Overall survival progression free survival and quality of life using FKSI-19 questionnaire will be recorded for each patient
This is an observational study among Danish patients treated for mRCC over a 6 year year period
Treatment of metastatic renal cell carcinoma mRCC is ineffective among 25 of patients However treatment still reduces patients quality of life
From clinical experience interindividual dose requirements vary greatly among patients with mRCC treated with tyrosine kinase inhibitors
The investigators expect this to partly be explained by great variation in the plasma concentration of treatment drugs Furthermore treatment failure among patients with mRCC treated with check point immunotherapy has not been fully investigated
RATIONALE
The few studies concerning plasma concentration measurement of tyrosine kinase inhibitors in patients with mRCC have found that a certain level of drug concentration is necessary for treatment efficacy The role of plasma concentration in side effects is yet unknown
Anti drug antibodies against the check point inhibitor ipilimumab has been shown to reduce efficacy and lead to treatment failure among patients with malignant melanoma Receptor polymorphism in CTLA-4 and PD-1 receptors in terms of efficacy have not yet been studied
A therapeutic drug interval for TKI treatment will allow for quicker and more precise dosing and early signs of treatment failure of checkpoint immunotherapy will allow for quicker change of therapy or define a subgroup of patients who will not benefit from checkpoint immunotherapy and therefore should be offered another effective treatment instead
HYPOTHESIS
1 Patients treated with TKIs for more than 6 months have an optimal plasma trough concentration Objective response rate progression free survival PFS overall survival OS and toxicity in these patients are favorable compared with pivotal phase III study results
2 Patients treated with CPI obtaining response have a higher plasma trough concentration value of ipilimumab and nivolumab than patients with progressive disease PD Patients treated with CPI who develop PD have a higher amount of ADA than patients with response to treatment
3 Certain polymorphisms in CTLA-4 and PD-1 are associated with poor outcome
4 UGT1A1 polymorphism is associated with improved survival despite dose reductions in patients treated with pazopanib
MATERIALS AND METHODS
All eligible TKI-patients will have blood samples drawn at each clinical visit during a 6-months period
The plasma concentration of TKIs will be measured with liquid chromatography-mass spectrometry at the Department of Clinical Biochemistry at Aarhus University Hospital
All eligible CPI-patients will have blood samples drawn from start CPI-treatment and during treatment until treatment failure or full treatment 2 years
Analysis of checkpoint immunotherapy will be be done using in-house bead-based assays anti-human IgG detection antibody and in-house developed flow cytometry-based assay at the Institute for Inflammation Research at Rigshospitalet
Overall survival progression free survival and quality of life using FKSI-19 questionnaire will be recorded for each patient
This is an observational study among Danish patients treated for mRCC over a 6 year year period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None