Clinical Trials Register

Summary
EudraCT Number:	2021-003311-26
Sponsor's Protocol Code Number:	77839
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-08-09
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2021-003311-26

A.3

Full title of the trial

DAVINCY trial: optimal Duration of (fos)aprepitant prophylaxis for nausea and Vomiting INduced by ChemotherapY in children: a double-blind placebo-controlled crossover randomized phase III trial’

DAVINCY: Verlengd gebruik (fos)aprepitant ter voorkoming van misselijkheid en braken veroorzaakt door chemotherapie in kinderen: een dubbel blind placebo gecontroleerd crossover gerandomizeerde fase 3 studie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

optimal Duration of (fos)aprepitant prophylaxis for nausea and Vomiting INduced by ChemotherapY in children

optimale duur van (fos)aprepitant profylaxe voor misselijkheid en braken geïnduceerd door chemotherapie bij kinderen

A.3.2

Name or abbreviated title of the trial where available

DAVINCY

A.4.1

Sponsor's protocol code number

77839

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Prinses Máxima Centrum
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMW
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Prinses Máxima Centrum
B.5.2	Functional name of contact point	Head Trial & Data Center
B.5.3	Address:
B.5.3.1	Street Address	Heidelberglaan 25
B.5.3.2	Town/ city	Utrecht
B.5.3.3	Post code	3584 CS
B.5.3.4	Country	Netherlands
B.5.6	E-mail	trialmanagement@prinsesmaximacentrum.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	IVEMEND
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	IVEMEND
D.3.2	Product code	IVEMEND
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	aprepitant
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	aprepitant
D.3.2	Product code	RVG 121086
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

prolonged anti emetic treatment

verlengde anti emetische behandeling

E.1.1.1

Medical condition in easily understood language

treatment of nausea and vomitting

behandeling van misselijkheid en braken

E.1.1.2

Therapeutic area

Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of prolonged duration of (fos)aprepitant prophylaxis on the prevention of delayed CINV (complete remission in the 24-72 hours after the final dose of chemotherapy) in children. The current 3-day regimen is compared to a regimen of (fos)aprepitant prophylaxis during the complete course of chemotherapy in the same patient in subsequent similar courses of chemotherapy, creating an intrapatient comparison of anti-emetic control.

Het evalueren van het effect van langdurige profylaxe met (fos)aprepitant op het voorkomen of minder aanwezig zijn van misselijkheid en braken veroorzaakt door chemotherapie bij kinderen. (uitblijven van misselijkheid en braken 24-72 uur na de laatste dosering chemotherapie). Het huidige 3-daagse regime wordt vergeleken met een regime van (fos)aprepitant profylaxe tijdens de volledige kuur van chemotherapie bij dezelfde patiënt in daaropvolgende vergelijkbare kuren van chemotherapie, waardoor een intra-patiënt vergelijking van anti-emetische controle ontstaat.

E.2.2

Secondary objectives of the trial

- To evaluate the effect of prolonged duration of (fos)aprepitant prophylaxis on the pre-vention of acute and overall chemotherapy induced nausea and vomiting (CINV) in children.
- To compare the effect of prolonged duration of (fos)aprepitant prophylaxis regarding the efficacy endpoint of no vomiting, regardless of rescue medication use, in the acute, delayed and overall phases.
- To assess the safety and tolerability of (fos)aprepitant according to a prolonged dosing regimen.
- To evaluate the pharmacokinetics of (fos)aprepitant during a prolonged dosing regi-men by constructing a population pharmacokinetics (PK) model.
- To assess the improvement of complaints of CINV in children during prolonged (fos)aprepitant dosing regimen by using the validated pediatric nausea assessment tool (PeNAT).17

Percentage patiënten dat:
- volledige respons bereikt tijdens chemotherapie tot 24 uur na de laatste dosis chemotherapie (acute fase)
- volledige respons bereikt tijdens zowel de acute als de vertraagde fase (algehele fase)
Tijd vanaf het begin van emetogene chemotherapie tot:
- de eerste episode van braken
- het eerste gebruik van reddingsmedicatie
Veiligheid van langdurig gebruik van (fos)aprepitant (AE's die door de onderzoekers als gerelateerd worden beschouwd)
Farmacokinetische (PK) parameters (d.w.z. klaring en distributievolume) en beïnvloedende PK-co variabelen als chemotherapeutica
Verbetering van CINV-klachten volgens de Pediatric Nausea Assessment tool (PeNAT) voor kinderen van 4-18 jaar
Kosteneffectiviteit van langdurig (fos)aprepitant doseringsschema

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The eligibility criteria are:
- Patients must be ≥ 6 months to ≤ 18 years at time of study entry. and weight ≥ 6kg
- Patients must have a documented malignancy.
- Patients need to receive moderate or highly emetogenic chemotherapy blocks, or chemotherapy not previously tolerated due to vomiting, for a minimum duration of 4 days.
- Chemotherapy schedules need to contain two similar courses of chemotherapy, which do not necessarily have to be consecutive courses.
- No symptomatic primary or metastatic CNS malignancy causing nausea or vomiting.
- Patients do not receive scheduled blocks of chemotherapy containing corticosteroids as part of anti-tumour treatment during the study period.
- Patients aged greater than 16y with a Karnofsky score of 60 or more or patients aged 16y or less with a Lansky Play performance score of 60 or more.
- Patient must have a life expectancy of 3 months or more.
- Patients must not use antiemetic treatment within 48h before treatment.
- Patients must not receive radiation therapy to the abdomen or pelvis in the week before treatment
- Patient must not use benzodiazepines or opioids initiated within 48h before treatment, except for single doses of triazolam, temazepam, or midazolam.
- Continuation of chronic benzodiazepine or opioid therapy is permitted provided it was initiated ≥48 hours prior to study drug administration.
- In patients on chronic warfarin, acenocoumarol, tolbutamide or phenytoin (me-tabolised by CYP2C9) therapy should be monitored closely during treatment with (fos)aprepitant and for 14 days following each course of (fos)aprepitant.
- No use of CYP3A4 substrates/inhibitors within 7 days, or no CYP3A4 inducers within 30 days of treatment
- Patient’s serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) ac-cording to age.
- Patient’s AST and ALT must be ≤ 5 x institutional ULN.
- Patient’s total bilirubin must be ≤ 1.5 x institutional ULN
- Patient must not have a history of QT prolongation
- Female patients of childbearing potential must have a negative urine or serum preg-nancy test confirmed prior to enrollment.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- Male and female patients of child-bearing potential must agree to use a highly effec-tive method of contraception approved by the investigator during the study, following the CTFG recommendations.
- Patients have no history of prior grade 3/4 allergic reaction to any of the study drugs
- Patients have no underlying gastrointestinal disease that may interfere with the ab-sorption of the medication

De geschiktheidscriteria zijn:
- Patiënten moeten ≥ 6 maanden tot ≤ 18 jaar oud zijn op het moment van deelname aan het onderzoek. En gewicht van ≥ 6kg.
- Patiënten moeten een gedocumenteerde maligniteit hebben.
- Patiënten moeten matige of sterk emetogene chemotherapie krijgen, of chemotherapie die voorheen niet werd verdragen vanwege braken, gedurende een minimumduur van 4 dagen.
- Chemotherapieschema's moeten twee vergelijkbare kuren chemotherapie bevatten, die niet noodzakelijkerwijs opeenvolgende kuren hoeven te zijn.
- Geen symptomatische primaire of gemetastaseerde maligniteit van het CZS die misselijkheid of braken veroorzaakt.
- Patiënten krijgen tijdens de onderzoeksperiode geen geplande blokken chemotherapie die corticosteroïden bevatten als onderdeel van een antitumorbehandeling.
- Patiënten ouder dan 16 jaar met een Karnofsky-score van 60 of meer of patiënten van 16 jaar of jonger met een Lansky Play-prestatiescore van 60 of meer.
- De patiënt moet een levensverwachting hebben van 3 maanden of meer.
- Patiënten mogen geen anti-emetische behandeling gebruiken binnen 48 uur voor de behandeling.
- Patiënten mogen in de week voor de behandeling geen bestraling van de buik of het bekken krijgen
- De patiënt mag geen benzodiazepines of opioïden gebruiken binnen 48 uur voor de behandeling start, behalve voor enkelvoudige doses triazolam, temazepam of midazolam.
- Voortzetting van chronische benzodiazepine- of opioïdtherapie is toegestaan op voorwaarde dat deze ≥48 uur voorafgaand aan de toediening van het onderzoeksgeneesmiddel is gestart.
- Bij patiënten die chronisch warfarine, acenocoumarol, tolbutamide of fenytoïne (gemetaboliseerd door CYP2C9) gebruiken, moet de therapie nauwlettend worden gevolgd tijdens de behandeling met (fos)aprepitant en gedurende 14 dagen na elke kuur met (fos)aprepitant.
- Geen gebruik van CYP3A4-substraten/-remmers binnen 7 dagen, of geen CYP3A4-inductoren binnen 30 dagen na behandeling
- Het serumcreatinine van de patiënt moet ≤ 1,5 x de institutionele bovengrens van normaal (ULN) zijn, in overeenstemming met de leeftijd.
- De AST en ALT van de patiënt moeten ≤ 5 x de institutionele ULN zijn.
- Het totale bilirubine van de patiënt moet ≤ 1,5 x de institutionele ULN zijn
- De patiënt mag geen voorgeschiedenis hebben van QT-verlenging
- Bij vrouwelijke patiënten die zwanger kunnen worden, moet een negatieve urine- of serumzwangerschapstest worden bevestigd voordat ze worden ingeschreven.
- Vrouwelijke patiënten met baby's moeten ermee instemmen hun baby's geen borstvoeding te geven tijdens deze studie.
- Mannelijke en vrouwelijke patiënten die zwanger kunnen worden, moeten ermee instemmen een zeer effectieve anticonceptiemethode te gebruiken die tijdens het onderzoek door de onderzoeker is goedgekeurd, volgens de CTFG-aanbevelingen.
- Patiënten hebben geen voorgeschiedenis van een eerdere allergische reactie van graad 3/4 op een van de onderzoeksgeneesmiddelen
- Patiënten hebben geen onderliggende gastro-intestinale aandoening die de absorptie van de medicatie kan verstoren

E.4

Principal exclusion criteria

See E3

zie E3

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients who achieve complete response (no vomiting, no retching and no use of rescue medication) during the 24-72 hours after the final dose of chemotherapy (delayed phase).

Percentage patiënten dat een volledige respons bereikt (geen braken, niet kokhalzen en geen gebruik van noodmedicatie) gedurende 24-72 uur na de laatste dosis chemotherapie (uitgestelde fase)

E.5.1.1

Timepoint(s) of evaluation of this end point

end of study

einde van de studie

E.5.2

Secondary end point(s)

Proportion of patients who:
- achieved complete response during the course of chemotherapy until 24h af-ter the final dose of chemotherapy (acute phase)
- achieved complete response during both the acute and delayed phase (overall phase)
Time from initiation of emetogenic chemotherapy to:
o the first vomiting episode
o the first rescue medication use
Safety of prolonged use of (fos)aprepitant (AEs considered related by the investiga-tors)
Pharmacokinetic (PK) parameters (i.e. clearance and volume of distribution) and in-fluencing PK co-variates as chemotherapeuticsImprovement of CINV complaints according to the Pediatric Nausea Assessment tool (PeNAT) for children aged 4-≤18 years
Cost-effectiveness of prolonged (fos)aprepitant dosing regimen

E.5.2.1

Timepoint(s) of evaluation of this end point

end of study

einde van de studie

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Treatment is not changing after finishing the study. We hope for future chemocourses we are able to improve antiemetic control in child oncology.

De behandeling verandert niet na het beëindigen van de studie. We hopen dat we met toekomstige chemokuren de anti-emetische controle in de kinderoncologie kunnen verbeteren.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-08-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-18

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials