Everolimus TDM to Predict Long Term Toxicity (Foresight)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03033186|
Recruitment Status : Unknown
Verified May 2017 by Maastricht University Medical Center.
Recruitment status was: Recruiting
First Posted : January 26, 2017
Last Update Posted : May 31, 2017
Metastatic (HR-positive, HER2-negative) breast cancer (BC), advanced or unresectable neuroendocrine tumours of pancreatic (pNET), gastrointestinal or lung origin and metastatic renal cell carcinoma (mRCC) are diseases with poor outcome. Everolimus increases patients' median progression-free survival (PFS) with 4.6 months in metastatic BC (mBC), 7 months in (p)NET and 3 months in mRCC. However, serious adverse events (AEs) occur frequently. This reduces effectiveness of everolimus, because AEs are managed with dose reductions, treatment interruptions or even complete discontinuation of everolimus.
Therapeutic-drug-monitoring (TDM) is used to adjust the prescribed daily dose, to maintain effective everolimus whole blood concentrations, with the lowest possible risk of AEs. While everolimus TDM has been common in transplantation medicine, it has not been implemented in oncology.
The importance of TDM in oncology is supported by previous research which showed that a 2-fold increased everolimus whole blood trough concentration was associated with a short-term risk of grade ≥ 3 pneumonitis, stomatitis and metabolic events. Moreover, an exposure-toxicity relationship of everolimus in patients with thyroid cancer was observed, since initial everolimus concentrations could be associated with early toxicity (< 12 weeks, e.g. stomatitis). However, the association between initial everolimus measurements and long-term AEs (≥12 weeks, e.g. pneumonitis, anorexia and anemia) of any grade and the need for everolimus dose reductions could not be made. Since levels ±>18 µg/L were associated with toxicity, the investigators assume that the upper therapeutic window of everolimus in the oncologic setting will be ±18 µg/L. Similarly, a tendency to improved PFS and overall survival was observed when Cmin in steady state was above 14.1 μg/L. This seems to be the lower limit of the therapeutic window.
Before consensus about the feasibility of everolimus TDM in the oncologic setting can be achieved, a number of questions (the knowledge gaps) need to be answered: 1. It is unknown whether everolimus whole blood trough levels (over time) predict long-term AEs. 2. The optimal concentration range for everolimus, with the treatment of mBC, mRCC, or (p)NET is unknown, especially the upper limit associated with toxicity. 3. It is unknown what everolimus concentration level is associated with the need for everolimus dose reductions.
|Condition or disease|
|Breast Cancer Renal Cell Carcinoma Pancreatic Neuroendocrine Tumour Gastrointestinal Neuroendocrine Tumour Neuroendocrine Neoplasm of Lung|
|Study Type :||Observational|
|Estimated Enrollment :||40 participants|
|Official Title:||Foreseeing the Moments of Occurrence of Everolimus Long-term Side Effects by Follow up of Trough Blood Concentrations|
|Actual Study Start Date :||May 16, 2017|
|Estimated Primary Completion Date :||September 1, 2018|
|Estimated Study Completion Date :||December 31, 2018|
Patients using everolimus as therapy for cancer: Advanced (Hormone-Receptor [HR]-positive, HER2-negative) breast cancer (BC), advanced or unresectable neuroendocrine tumours of pancreatic (pNET), gastrointestinal or lung origin and metastatic renal cell carcinoma (mRCC)
- Everolimus TDM to predict long-term toxicity [ Time Frame: Up to 2 year ]The difference in percentage of patients with a high everolimus trough level (i.e. > 18 ng/mL) experiencing NCI-CTCAE v4.0 grade 2, 3 or 4 late AEs (i.e. toxicity reported from ≥ 12 weeks onward, e.g. pneumonitis, anorexia, anemia) compared to participants with lower trough concentrations.
- Everolimus TDM to predict short-term toxicity [ Time Frame: Up to 2 year ]The difference in percentage of patients with a high everolimus trough level (i.e. > 18 ng/mL) experiencing NCI-CTCAE v4.0 grade 2, 3 or 4 early AEs (i.e. toxicity reported from < 12 weeks, e.g. stomatitis) compared to participants with lower trough concentrations.
- Correlation everolimus concentration DBS from fingerprick with whole blood from venipuncture [ Time Frame: Up to 2 year ]To define the correlation between everolimus concentration measured in whole blood after a venipuncture as compared to the everolimus concentration measured from dried capillary blood extracted from the Whatman filterpaper of the DBS.
- Correlation everolimus concentration DBS from fingerprick with DBS spiked with whole blood from venipuncture [ Time Frame: Up to 2 year ]To define the correlation between everolimus concentration collected with DBS from a finger prick and DBS paper spiked with a drop of everolimus from venipunctured whole blood extracted from the Whatman filterpaper of the DBS.
- Everolimus TDM to predict dose reductions [ Time Frame: Up to 2 year ]To define the correlation between the everolimus trough levels (over time) between patients using full dose everolimus (e.g. 10 mg once daily) and patients using everolimus in a reduced dose (e.g. 2,5 or 5 mg once daily) at each moment of blood sampling in time.
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03033186
|Contact: S. Croes, PharmD PhD||(+31)43 firstname.lastname@example.org|
|Contact: L. Knapen, PharmD||(+31)43 email@example.com|
|Maastricht University Medical Centre||Recruiting|
|Maastricht, Limburg, Netherlands, 6202 AZ|
|Contact: S. Croes, PharmD, PhD (+31)43 3871431 firstname.lastname@example.org|
|Contact: L.M. Knapen, MSc (+31)43 3871881 email@example.com|
|Principal Investigator: S. Croes, PharmD PhD|
|Principal Investigator: L.M. Knapen, MSc|
|Sub-Investigator: A. Bast, MD PhD Prof|
|Sub-Investigator: V.C.G. Tjan-Heijnen, MD PhD Prof|
|Sub-Investigator: N.P. van Erp, PharmD PhD|
|Sub-Investigator: M. de Boer, MD PhD|
|Sub-Investigator: I.J.H. Vriens, MD|
|Sub-Investigator: M.J.B. Aarts, MD PhD|
|Principal Investigator:||S. Croes, PharmD, PhD||Maastricht University Medical Centre+|