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De Optimal studie: Optimaliseren van Everolimus behandeling door het splitsen van innamemomenten.


- candidate number20892
- NTR NumberNTR4908
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR7-nov-2014
- Secondary IDs2014-004833-25 EudraCT
- Public TitleDe Optimal studie: Optimaliseren van Everolimus behandeling door het splitsen van innamemomenten.
- Scientific TitleThe OPTIMAL study:
Optimizing Performance of afiniTor by splitting Intake Moments and decreasing Adverse events whilst maintaining outcome quaLity.
- ACRONYMOPTIMAL
- hypothesisThe 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.
- Healt Condition(s) or Problem(s) studiedBreast cancer, HER2/neu negative tumor
- Inclusion criteria1.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 advanced hormone positive, HER2 negative, breast cancer for which everolimus in combination with exemestane is considered standard of care.
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 criteria1.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
- mec approval receivedno
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlActive
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-mei-2014
- planned closingdate30-jun-2015
- Target number of participants10
- Interventions5 mg BID Everolimus plus 25 mg QD Exemestane vs 10 mg QD Everolimus plus 25 mg QD Exemestane
- Primary outcomePharmacokinetics of 10 mg QD vs 5 mg BID Everolimus: evaluated PK parameters will be a.o. Cmax/Cmin ratio, AUC, Cmax, Cmin, Tmax.
- Secondary outcomeIncidence and severity of stomatitis and other adverse events between the two dosing schedules, according to CTC-AE v4.03.
- TimepointsAfter 2 weeks of treatment (steady state) in each treatment arm.
- Trial web site
- statusplanned
- CONTACT FOR PUBLIC QUERIES R.B. Verheijen
- CONTACT for SCIENTIFIC QUERIESDr. N. Steeghs
- Sponsor/Initiator Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI AVL)
- Funding
(Source(s) of Monetary or Material Support)
Novartis
- Publications
- Brief summaryThe 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.
- Main changes (audit trail)20-mrt-2016:

- Inclusion criterion changed to: “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).
- Exclusion criterion added: "CT or other tumour response evaluation planned during the 4 weeks of the trial"
- Erasmus University Medical Center was added as trial site.
- RECORD7-nov-2014 - 20-mrt-2016


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