No registrations found.
ID
Source
Brief title
Health condition
Advanced hormone positive, HER2 negative, breast cancer.
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics of 10 mg QD vs 5 mg BID Everolimus: evaluated PK parameters will be a.o. Cmax/Cmin ratio, AUC,
Cmax, Cmin, Tmax.
Secondary outcome
Incidence and severity of stomatitis and other adverse events between the two dosing schedules, according to CTC-AE
v4.03.
Background summary
The hypothesis of this study is that dosing everolimus 5mg twice daily(BID) instead of 10 mg once daily (QD) decreases
the incidence of side effects, as a result of a lower Cmax while maintaining Cmin and AUC.
In clinical practice a substantial number of
patients has dose limiting or quality of life reducing side effects.
Some everolimus side effects (like stomatitis) may be Cmax driven. Stomatitis (any grade) occurs in more than half of all patients treated with 10 mg Everolimus QD. Considering the pharmacological properties of everolimus, we hypothesize that this decrease in Cmax (while maintaining Cmin and AUC) can be established by dividing the standard everolimus tablets over the day (upholding the same daily dose).
We suggest to perform a study measuring everolimus pharmacokinetics during twice daily dosing of 5 mg of standard
everolimus tablets and compare this with PK data derived from once daily dosing of 10 mg of standard everolimus tablets.
If the Cmax in the BID schedule is reduced whilst maintaining Cmin and AUC, spreading intake moments of everolimus
over the day might reduce adverse events without compromising treatment efficacy.
Study objective
The hypothesis of this study is that dosing everolimus 5mg twice daily(BID) instead of 10 mg once daily (QD) decreases
the incidence of side effects, as a result of a lower Cmax while maintaining Cmin and AUC.
Study design
After 2 weeks of treatment (steady state) in each treatment arm.
Intervention
5 mg BID Everolimus plus 25 mg QD Exemestane vs 10 mg QD Everolimus plus 25 mg QD Exemestane
Netherlands Cancer Institute - Antoni van Leeuwenhoek
R.B. Verheijen
Plesmanlaan 121
Amsterdam 1066CX
The Netherlands
-
r.verheijen@nki.nl
Netherlands Cancer Institute - Antoni van Leeuwenhoek
R.B. Verheijen
Plesmanlaan 121
Amsterdam 1066CX
The Netherlands
-
r.verheijen@nki.nl
Inclusion criteria
1.Age >18 years;
2.Able and willing to give written informed consent;
3.Able and willing to undergo blood sampling for PK analysis;
4.Histopathologically confirmed cancer for which everolimus is considered standard of care, who will start with or are already receiving everolimus therapy (breast cancer patients will also receive exemestane (in accordance with the summary of product characteristics), other patients will receive everolimus monotherapy).
5.Minimal acceptable safety laboratory values
a.ANC of > 1.5 x 10^9 /L
b.Platelet count of > 100 x 10^9 /L
c.Hepatic function as defined by serum bilirubin ¡Ü 1.5 x ULN, ASAT and ALAT ¡Ü2.5 x ULN
d.Renal function as defined by serum creatinine ¡Ü1.5 x ULN or creatinine clearance >50 mL/min (by Cockcroft-
Gault formula);
Exclusion criteria
1.Woman who are pregnant or breast feeding;
2.Known hypersensitivity to any of the study drugs or excipients;
3.Unable or unwilling to undergo pharmacokinetic sampling;
4.Use of any concomitant medication (including OTC and herbal medication) which may induce or inhibit function
of CYP3A4, including but not limited to efavirenz, etravirine, nevirapine, rifampicine, boceprevir, claritromycine,
elvitegravir, erytromycine, fluconazol, itraconazol, ketoconazol, posaconazol, telaprevir, verapamil, cyclosporine,
voriconazol, dexamethason, St John¡'s Wort and grapefruit juice;
5.Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion
of the investigator would impair study compliance;
6.Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory
finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug
or puts the patient at high risk for treatment-related complications;
7.Legal incapacity;
8.CT or other tumour response evaluation planned during the 4 weeks of the trial.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
NTR-new | NL4702 |
NTR-old | NTR4908 |
Other | EudraCT : 2014-004833-25 |