TDM for Optimized Outcome in Patients With mRCC.

April 28, 2026 updated by: Niels Fristrup

Therapeutic Drug Monitoring for Optimized Outcome in Patients With Metastatic Renal Cell Carcinoma

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. It furthermore holds microbiome characterization of CPI-treated patients.

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 (CPI). Moreover, polymorphisms in the UGT1A1 gene will be correlated with the pazopanib treatment dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 (Cmin). 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. We hypothesize that it is possible to elucidate a therapeutic interval for the TKIs examined in the study
  3. Patients treated with CPI obtaining response have a higher plasma trough (Cmin) 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.
  4. Certain polymorphisms in CTLA-4 and PD-1 are associated with poor outcome.
  5. UGT1A1 polymorphism is associated with improved survival despite dose reductions in patients treated with pazopanib.
  6. The microbiome composition correlates with treatment outcome of CPI.
  7. CT DNA measurement may be marker of disease activity and treatment effect.

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 and fecal swap performed from start CPI-treatment and during treatment until treatment failure or full treatment (2 years).

Analysis of blood and microbiome from patients receiving 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.

TKI STUDY AIM:

To compare the trough plasma concentrations (Cmin) of TKIs in patients with mRCC having stable disease with those experiencing toxicity, treatment failure, and stable disease or regression, respectively to identify the optimal plasma concentration level.

CPI STUDY AIMS:

Aim 1: To compare the trough plasma concentration of CPI with toxicity and outcome in patients with mRCC to identify the optimal plasma concentration level.

Aim 2: To measure the concentration of circulating ADA against immune-checkpoint inhibitors ipilimumab and nivolumab in patients with mRCC and correlate best objective response to the concentration of ADA.

Aim 3: To compare polymorphisms in CTLA-4 and PD-1 and correlate findings with clinical outcomes in patients with mRCC treated with ipilimumab and/or nivolumab.

Aim 4: To delineate the microbiome in mRCC patients treated with immunotherapy and associating it to response and survival.

Aim 5: To use circulating tumor DNA as a marker for disease activity and treatment effect in mRCC patients.

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 7 year year period.

Perspectives of TDM in TKI patients:

Determining a therapeutic interval for TKIs could optimize treatment for mRCC patients by:

  1. Titrating up doses for patients with insufficient levels to reduce cancer progression risk.
  2. Titrating down doses for overdosed patients to limit toxicity and costs.
  3. Monitoring patients on intermittent therapy interacting with TKI treatment. These results may extend to other cancer types using TKIs.

Perspectives for TDM in CPI patients:

A therapeutic interval and characterisation of treatment failure of CPI will most likely optimize treatment for patients with mRCC for the following reasons:

  1. Patients who receive an insufficient dose and therefore have a potential risk of cancer progression can be titrated up to a sufficient level.
  2. Patients who develop serious adverse events are overdosed and can be titrated down to a sufficient level - limiting toxicity and cost.
  3. Patients who develop ADAs or have insufficient binding between CPI and T-lymphocytes can switch to another effective therapy before cancer progression.

These results will likely extrapolate to other cancer types as CPI is increasingly being used for other cancer diagnoses.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
    • Danmark
      • Aarhus, Danmark, Denmark, 8200
        • Recruiting
        • Department of Oncology, Aarhus University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Adult patients in Denmark with medically treated metastatic renal cell carcinoma. Patients are treated in the two biggest oncology departments in Denmark, Aarhus and Herlev.

Description

Inclusion Criteria:

  • Patients in Denmark with medically treated metastatic renal cell carcinoma.

Exclusion Criteria:

  • No written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort 1
Patients treated for metastatic renal cell carcinoma in Denmark over a 6-year period.
Other: Measurement of concentration of active metabolite in cancer treatment.
Medical treatment for metastatic renal cell carcinoma with axitinib, cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib and ipilimumab and nivolumab.
Other Names:
  • Measurement of autoantibodies and receptor polymorfia for CTLA-4 and PD-1 inhibition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 12 months follow-up for each patient.
Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.
12 months follow-up for each patient.
Progression free survival (PFS)
Time Frame: 12 months follow-up for each patient.
According to the RECIST v1.1
12 months follow-up for each patient.
Quality of life according to NCCN-FACT FKSI-19.
Time Frame: 12 months follow-up for each patient.

National Comprehensive Cancer Network/ Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (NCCN-FACT FKSI-19).

19 items, each item scored on a 5 point Likert-scale, covering cancer quality of life.
12 months follow-up for each patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In pts treated with pazopanib: UGT1A1 genetic polymorphism
Time Frame: At baseline
TA6/TA6, TA6/TA7 or TA7/TA7
At baseline
Amount of antidrug antibodies (ADAs) developed.
Time Frame: 12 months follow-up for each patient.
In patients treated with ipilimumab/nivolumab
12 months follow-up for each patient.
SNP-genotype of PD-1 and CTLA-4 receptors reported as proportion of patients with pp-, pq- and qq-genotype respectively.
Time Frame: 12 months follow-up for each patient.
In pts treated with ipilimumab/nivolumab
12 months follow-up for each patient.
Fecal swap
Time Frame: 12 months follow-up for each patient
Measuring the microbiome composition, from start and during CPI therapy
12 months follow-up for each patient
Measuring CT DNA in patiets receiving nivolumab and ipilimumab
Time Frame: 12 months follow-up for each patient
CT DNA
12 months follow-up for each patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Niels Fristrup

Collaborators

Rigshospitalet, Denmark
Herlev Hospital

Investigators

  • Principal Investigator: Niels Fristrup, MD, PhD, University of Aarhus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2020

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

August 31, 2029

Study Registration Dates

First Submitted

November 20, 2020

First Submitted That Met QC Criteria

December 2, 2020

First Posted (Actual)

December 9, 2020

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TDM mRCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Cancer

Clinical Trials on Measurement of concentration of active metabolite in cancer treatment.

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bulgaria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe