Clinical Trials Register

Summary
EudraCT Number:	2015-004304-27
Sponsor's Protocol Code Number:	RIST-rPB-2015-P
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-01
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2015-004304-27

A.3

Full title of the trial

Prospective pilot trial to assess a multimodal molecular targeted therapy in children, adolescent and young adults with relapsed or refractory high-grade pineoblastoma

A.3.1

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

A clinical study to investigate the efficiency of a novel anticancer
medication against pineoblastoma in children, adolescent and
young adults in whom the tumor relapsed or was refractory to standard
care

A.3.2

Name or abbreviated title of the trial where available

RIST-rPB-2015-P

A.4.1

Sponsor's protocol code number

RIST-rPB-2015-P

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	University Hospital of Regensburg
B.1.3.4	Country	Germany
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	Deutsche Krebshilfe (DKH)
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital of Regensburg
B.5.2	Functional name of contact point	SPOH Dokumentation
B.5.3	Address:
B.5.3.1	Street Address	Franz-Josef-Strauss-Allee 11
B.5.3.2	Town/ city	Regensburg
B.5.3.3	Post code	93053
B.5.3.4	Country	Germany
B.5.4	Telephone number	+490941944-2063
B.5.5	Fax number	+490941944-2068
B.5.6	E-mail	kinderonkologie@ukr.de

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	Sprycel
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers-Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Sprycel
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Temomedac
D.2.1.1.2	Name of the Marketing Authorisation holder	Medac
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Temomedac
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: 3
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	Rapamune
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Rapamune
D.3.2	Product code	PF-00835135
D.3.4	Pharmaceutical form	Oral solution
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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: 4
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	Irinomedac
D.2.1.1.2	Name of the Marketing Authorisation holder	Medac
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Irinomedac
D.3.4	Pharmaceutical form	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: 5
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	Rapamune
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Rapamune
D.3.2	Product code	PF-00835135
D.3.4	Pharmaceutical form	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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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: 6
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	Sprycel
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers-Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Sprycel
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

Relapsed or refractory high-grade pineoblastoma

Rezidiviertes oder therapierefraktäres hochgradiges Pineoblastom

E.1.1.1

Medical condition in easily understood language

Relapsed or refractory high-grade pineoblastoma

Rezidiviertes oder therapierefraktäres hochgradiges Pineoblastom

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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

The primary objective of this trial is the evaluation of response of rPB in children, adolescents and young adults to the RIST protocol.

Das primäre Studienziel ist die Evaluation des Ansprechens von rPB bei Kindern, Jugendlichen und jungen Erwachsenen auf das RIST-Protokoll

E.2.2

Secondary objectives of the trial

Secondary objectives are
• Overall survival
• Response rate (RR) after 4 and 8 courses of irinotecan and temozolomide in the RIST treatment arm
• Toxicity of this combination of drugs in children, adolescents and young adults with rPB
• Duration of response of this treatment regimen
• Safety and tolerability of the investigational treatment
• Assessment of quality of life

Sekundäre Ziele sind:
• Gesamtüberleben (OS)
• Response Rate (RR) nach 4 und 8 Kursen Irinotecan und Temozolomid im RIST-Behandlungsarm
• Evaluation der Toxizitäten dieser Arzneimittel-Kombination bei Kindern, Jugendlichen und jungen Erwachsenen mit rNB
• Ansprechdauer des RIST Behandlungsregimes
• Sicherheit und Verträglichkeit des RIST-Behandlungsregimes
• Bewertung der Lebensqualität

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients with relapsed high-grade pineoblastome (=rPB)
and all of the following criteria will be considered for admission to the clinical trial:
• Children, adolescents and young adults 0 months to 25 years
• Signed written informed consent (patient or his/her parents/legal guardian)
• Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug. The first pregnancy test must be performed within 10-14 days prior to the start of the study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive the study drug until the investigator has verified that the results of these pregnancy tests are negative.
• Females of childbearing age must comply with the institutional standards of birth control with a pearl index <1%. Contraception must be started at least four weeks before the start of the investigational therapy.
• Females of childbearing age must be willing to abstain from breastfeeding for the duration of the clinical trial and for at least 30 days after discontinuation of the clinical trial.
• Males must agree not to father a child and must use latex condom during any sexual contact with women of childbearing age during and for 6 months after therapy ends or is stopped, even if they have undergone successful vasectomy.
• Willing and able to complete the clinical trial procedures, as described in the protocol
• Non-smoker for at least the previous 3 months. Smoking is not allowed during the entire study period
• Abstain from alcohol within the last 24 hours before screening and before admission to the clinical trial center as well as during the entire clinical trial. The regular daily ethanol intake has to be less than 20g/day for at least the previous three months.
• Patients are required to have an absolute neutrophil count (ANC) ≥500/µL, hemoglobin ≥8g/dL (transfusion permitted), and an unsupported platelet count ≥30,000/µL unless:
- extensive bone marrow involvement was documented
- patient is refractory or relapsed early after primary therapy

Patienten mit rezidiviertem hochgradigen Pineoblastom oder progredienter Erkrankung während der Ersttherapie (=rNB),die alle folgenden Kriterien erfüllen:

• Kinder, Jugendliche und junge Erwachsene im Alter von 0 Monaten bis <25 Jahren
• Vorliegen einer gültigen Einverständniserklärung zur Teilnahme an der Studie
• Negativer Schwangerschaftstest vor Einnahme der Studienmedikation bei weiblichen Studienteilnehmern in gebärfähigem Alter. Ein erster Schwangerschaftstest sollte 10-14 Tage vor Beginn der Einnahme der Studienmedikation erfolgen. Der zweite Test muss innerhalb von 24 Std. vor Einnahme der Studienmedikation erfolgen. Ein Erhalt der Studienmedikation erfolgt erst nach Überprüfung des Prüfarztes auf Nichtvorliegen einer Schwangerschaft.
• Weibliche Studienteilnehmer müssen eine Methode zur Empfängnisverhütung mit einem Pearl-Index von <1% anwenden. Der Beginn dieser Empfängnisverhütung muss mindestens 4 Wochen vor der ersten Einnahme der Studienmedikation erfolgen.
• Frauen in gebärfähigem Alter dürfen während der gesamten Studiendauer bis einschließlich 30 Tage nach Studiendauer nicht stillen.
• Männliche Studienteilnehmer müssen zustimmen, während der Laufzeit der Studie und bis 6 Monate nach Beendigung der Studientherapie, kein Kind zu zeugen und Latex-Kondome bei jedem sexuellen Kontakt mit Frauen in gebärfähigem Alter zu benutzen. Dies gilt auch, wenn eine erfolgreiche Vasektomie durchgeführt wurde.
• Bereitschaft des Patienten dem Behandlungsplan protokollgemäß zu nachzukommen.
• Nichtraucher für mindestens 3 Monate vor Beginn der Studientherapie. Rauchen ist während der gesamten Studientherapie nicht erlaubt.
• Kein Alkoholgenuss innerhalb der letzten 24 Stunden vor Screening und Aufnahme in das Prüfzentrum ebenso während der gesamten klinischen Studie. Während der vorangegangenen drei Monate sollte der Alkoholkonsum 20g/Tag nicht überschritten haben.
• Absolute Neutrophilenzahl (ANC) ≥500/ µL, Hb ≥8 g/dL (Transfusion erlaubt) und Thrombozytenzahl (ohne Transfusion) ≥30,000/µL es sei denn:
- der Patient ist therapierefraktär auf Ersttherapie oder es liegt ein Frührezidiv nach Ersttherapie vor.

E.4

Principal exclusion criteria

Patients presenting with any of the following criteria will not be included in this clinical trial:
• Pregnancy, nursing
• Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadine derivatives or low molecular weight heparin derivatives, LMWH)
• Patients with cardiac arrhythmias especially prolonged QT
• Patients with chronic inflammatory bowel diseases and/or bowel obstruction
• Patients with bilirubin serum levels 1,5 fold above the upper normal limit
• Vaccination with a live virus vaccine during the clinical trial
• Impaired liver function and/or impaired renal function (hepatic and renal index parameter two times above normal range; see below)
• Potentially unreliable subjects, probably non compliant subjects and those judged by the investigator to be unsuitable for the study
• Doubts about the patient’s cooperation
• Any contraindications or known hypersensitivity to the IMPs or to any of the other components: (see SPC ”Fachinformation”)
• Known allergic reactions to the treatment medication
• Patients who were treated with radiation and/or chemotherapy for any other oncological condition
• Participation in any other interventional phase I to III trial
• Sexually active patients who refuse to use contraception according to the institutional requirements
• Patients with extremely poor general condition (Karnofsky or Lansky score <50%)
• Neutrophil count (ANC) <500/µL, hemoglobin <8g/dL (transfusion permitted), and an unsupported platelet count <30 000/µL
• 12-lead ECG with QTc>500 msec / QTc>60 msec baseline
• Patients with hepatitis B reactivation

Patienten, die eines der folgenden Kriterien erfüllen, werden nicht in die klinische Studie eingeschlossen:
• Schwangerschaft, Stillzeit
• Patienten mit thrombotischen Ereignissen und die aufgrund dessen Antikoagulantien (d.h. Coumarin-Derivate oder niedermolekulares Heparin, LMWH) erhielten
• Patienten, die unter Arrhythmien leiden, besondere eine verlängerte QT-Zeit aufweisen
• Patienten mit chronisch entzündlichen Darmerkrankungen und/oder Darmverschluss
• Patienten, deren Bilirubin-Serumspiegel 1,5 mal höher als der Normwert ist
• Impfung mit Lebendviren während der Laufzeit der Studie
• Beeinträchtigte Leberfunktion und/oder gestörte Nierenfunktion (Leber- und Nierenwerte zweimal über Normwert)
• Personen mit mangelnder Compliance und die vom Prüfer als nicht zulässig für die Studie beurteilt wurden
• Bei Zweifeln über die Kooperation des Patienten
• Alle die Prüfmedikamente oder irgendeinen der anderen Inhaltsstoffe (siehe beigefügte Fachinformation) betreffende Kontraindikationen oder bekannte Überempfindlichkeiten
• Bekannte allergische Reaktion auf die verabreichten Medikation
• Patienten, die bereits aufgrund anderer onkologischer Vorerkrankung mit Chemotherapie und/oder Strahlentherapie vorbehandelt sind
• Teilnahme an einer anderen interventionellen Studie der Phasen I bis III
• Sexuell aktive Patienten, die sich einer effektiven Kontrazeption verweigern
• Patienten mit sehr schlechtem klinischen Allgemeinzustand (Karnofsky oder Lansky Scores <50%)
• Absolute Neutrophilenzahl (ANC) <500/ µL, Hb <8 g/dL (Transfusion erlaubt) und Thrombozytenzahl (ohne Transfusion) <30,000/µL
• EKG mit QTc>500 msec / QTc>60 msec baseline
• Patienten mit Hepatitis-B Reaktivierung

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is progression-free survival (PFS), which is defined as the time interval between randomization and date of progression according to
• Imaging criteria to
o MRI, CT or
o CSF evaluations
or
• date of death of any cause.
Patients with no progression until end of study or patients lost to follow up will be classified as censored cases at the latest date they will be confirmed to be progression free.

Der primäre Endpunkt ist progressionsfreies Überleben (PFS), definiert als das Zeitintervall zwischen Behandlungsbeginn und Progressionsdatum, entsprechend
• Bildgebenden Kriterien
o MRT, CT
oder
o Beurteilung des Liquors
oder
• Datum des Todes jeglicher Ursache
Patienten ohne Progress bis Studienende oder bei Patienten, die lost-to-follow-up sind, werden als zensierte Fälle klassifiziert und als Berechnungsgrundlage wird das letzte Datum gewählt, an dem die Pat. bestätigt progressionsfrei waren.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint of the study, progression free survival will be investigated after 8 completed I/T-courses (approx. 20 weeks). The patients are then followed in 3-monthly intervals until one year after medical treatment was finished.

Der primäre Endpunkt der Studie, das progressionsfreie Überleben, wird nach 8 vollendeten I/T-Kursen (ca. 20 Wochen) beurteilt. Anschließend erfolgt eine Nachbeobachtung in vierteljährlichem Abstand bis 1 Jahr nach Ende der Therapie.

E.5.2

Secondary end point(s)

• Overall survival (OS)
• Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm
• Duration until adequate response to this treatment regimen
• Assessment of quality of life (Lansky and Karnofsky Scores)

• Gesamtüberleben (OS)
• Therapieansprechen nach 4 und 8 Kursen I/T und 1 Jahr Follow-Up im RIST-Arm
• Dauer bis zum Therapieansprechen in diesem Therapieregime
• Bewertung der Lebensqualität (Lansky und Karnofsky Scores)

E.5.2.1

Timepoint(s) of evaluation of this end point

-after 4 completed I/T-courses (8 weeks), after 8 completed 8 I/T-courses (20 weeks) and in 3-monthly intervals until one year after medical treatment was finished.
- quality of life will be investigated before start of treatment and then in 6-monthly intervals until one year after medical treatment was finished.

- nach 4 vollendeten I/T-Kursen (8 Wochen), nach 8 vollendeten I/T-Kursen (20 Wochen) und anschließend in vierteljährlichem Abstand bis ein Jahr nach Ende der Therapie beurteilt.
- die Lebensqualität wird vor Beginn der Therapie und nachfolgend in halbjährlichem Abstand bis 1 Jahr nach Ende der Therapie beurteilt.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Pilotstudie

Pilot trial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

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)

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children under the age of comprehension of the trial and therefore unable to give constent or even assent

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)

Patients in the trial are followed according to the guidelines of the GPOH (German Pediatric Oncology Group) for 10 years outlined in the protocol

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Gesellschaft für pädiatrische Onkologie und Hämatologie
G.4.3.4	Network Country	Germany

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-04-30

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Orphan Designation Number:
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