Clinical Trials Register

Summary
EudraCT Number:	2021-000087-30
Sponsor's Protocol Code Number:	Swecranio1-21
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-04-14
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

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2021-000087-30

A.3

Full title of the trial

Neoadjuvant and postoperative treatment with dabrafenib and trametinib
for papillary craniopharyngioma

Neoadjuvant och postoperativ behandling med dabrafenib och trametinib
vid papillärt kraniofaryngeom

A.3.1

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

Treatment with the drugs dabrafenib and trametinib before or after
operation for the tumour papillary craniopharyngioma

Behandling med medicinerna dabrafenib och trametinib före eller efter
operation av tumören papillärt kraniopfaryngeom

A.4.1

Sponsor's protocol code number

Swecranio1-21

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	Skane University Hospital, Dept of Endocrinology
B.1.3.4	Country	Sweden
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	Region Skåne, Skane University Hospital
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Skane University Hospital, Dept of Endocrinology
B.5.2	Functional name of contact point	Endokrinmottagningen
B.5.3	Address:
B.5.3.1	Street Address	Lasarettsgatan 15
B.5.3.2	Town/ city	Lund
B.5.3.3	Post code	22241
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46461710007123
B.5.6	E-mail	eva-marie.erfurth@med.lu.se

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	Tafinlar
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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.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	Mekinist
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Film-coated tablet
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Papillary craniopharyngioma

Papillärt kraniofaryngeom

E.1.1.1

Medical condition in easily understood language

Craniopharyngeoma, benign tumour near the pituitary and hypothalamus

Kraniofaryngeom, en godartad tumör belägen vid hypofysen och hypothalamus

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	LLT
E.1.2	Classification code	10084813
E.1.2	Term	Papillary craniopharyngioma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate tumour response measured as reduction in tumour volume on MRI for patients with papillary craniopharyngioma on treatment with dabrafenib and trametinib.

Att utvärdera tumörrespons i form av minskad tumörvolym på MR för patienter med papillärt kraniofaryngeom vid behandling med dabrafenib och trametinib.

E.2.2

Secondary objectives of the trial

To evaluate treatment with dabrafenib and trametinib for the following aspects:
- response according to RECIST
- response duration for patients who are treated without subsequent surgery
- number of patients that become operable after neoadjuvant treatment
- progression free survival after 1 and 2 years
- quality of life during and after treatment
- the effect of treatment on vision, cognition and hypothalamic function

Att utvärdera behandling med dabrafenib och trametinib för följande aspekter:
- response enligt RECIST
- responsduration för patienter som behandlas utan efterföljande kirurgi
- hur många patienter som blir operabla efter neoadjuvant behandling
- progressionsfri överlevnad efter 1 och 2 år
- livskvalitet under och efter behandling
- behandlingens effekt på syn, kognition, hypotalamisk påverkan

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically verified papillary craniopharyngioma
2. BRAFmut V600E, verified immunohistochemically and with sequencing.
3. Newly diagnosed tumour or recurrence after previous surgery, where additional surgery would give serious or permanent sequelae.
4. Age over 18 years.
5. Performance status acccording to ECOG 0-2
6. Adequate organ function

1. Patienter med histologiskt verifierat papillärt kraniofaryngeom.
2. BRAFmut V600E, verifierad immunhistokemiskt och med molekylärgenetisk analys
3. Nydiagnosticerad tumör, eller recidiv efter tidigare kirurgi, där kirurgi inte bedöms kunna utföras radikalt utan risk för allvarliga eller permanenta sekvele.
4. Ålder över 18 år
5. Funktionsstatus enligt ECOG 0-2
6. Adekvat organfunktion

E.4

Principal exclusion criteria

1. Ongoing treatment with prohibited drugs (strong inducers of CYP2C8 or CYP3A4).
2. Known cardiovascular disease where MEK-inhibitor is contraindicated, e g serious heart failure, increased QTc time, uncontrolled arrythmia, recent myocardial infarction, uncontrolled hypertension
3. Active bleeding
4. Thromboembolic event last 6 months
5- Known serious ocular disease
6. Surgery last 3 weeks
7. Cohort b: radiotherapy last 3 months

1. Pågående behandling med icke-tillåtna läkemedel, (starka inducerare av CYP2C8 eller CYP3A4)
2. Känd hjärtkärlsjukdom där behandling med MEK-hämmare bedöms olämplig, tex allvarlig hjärtsvikt, förlängning av QTc-tid, okontrollerad arrytmi, nyligen genomgången hjärtinfarkt, okontrollerad hypertoni.
3. Aktiv blödning
4. Tromboembolisk sjukdom senaste 6 månader
5. Känd allvarlig ögonsjukdom
6. Kirurgi inom senaste 3 veckor.
7. För kohort b: strålbehandling inom senaste 3 månader

E.5 End points

E.5.1

Primary end point(s)

To evaluate tumour response measured as reduction in tumour volume on MRI for patients with papillary craniopharyngioma on treatment with dabrafenib and trametinib.

Att utvärdera tumörrespons i form av minskad tumörvolym på MR för patienter med papillärt kraniofaryngeom vid behandling med dabrafenib och trametinib.

E.5.1.1

Timepoint(s) of evaluation of this end point

5 years after initiation of study

5 år efter att studien startats

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

5 years after study initiation

5 år efter att studien startats

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

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

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Sista patientens sista besök

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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)

The patients will receive standard of care after end of participation in the trial

Patienterna kommer att erhålla standardbehandling efter att studiedeltagandet avslutats.

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

2021-07-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-09

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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