Clinical Trials Register

Summary
EudraCT Number:	2004-002803-34
Sponsor's Protocol Code Number:	Cetcapox-RT_31.08.2004
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2004-11-25
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

Germany - PEI

A.2

EudraCT number

2004-002803-34

A.3

Full title of the trial

Phase I/II-Studie
Praeoperative Radiochemotherapie mit Capecitabin plus Oxaliplatin und Cetuximab beim lokal fortgeschrittenen Rektumkarzinom im UICC-Stadium II und III

A.3.2

Name or abbreviated title of the trial where available

Cetcapox-RT

A.4.1

Sponsor's protocol code number

Cetcapox-RT_31.08.2004

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Klinik und Poliklinik fuer Strahlentherapie, Universität Erlangen-Nürnberg
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
D.2.1.1.1	Trade name	Erbitux
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck KGaA
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	Erbitux
D.3.2	Product code	EMD271786
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody
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	Information not present in EudraCT
D.2.1.1.1	Trade name	Xeloda
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration 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	Xeloda
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Information not present in EudraCT
D.2.1.1.1	Trade name	Eloxatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Synthelabo
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	Oxaliplatin
D.3.2	Product code	-
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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

Rektumkarzinom

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

Die Phase-I/II-Studie soll Effektivität und Tolerabilität einer innovativen Chemotherapie mit einem oralen 5-FU-Derivat (Capecitabin, i.f. Cap) plus Oxaliplatin (i.f. Ox) in Verbindung mit dem EGFR-Antikörper Cetuximab im Rahmen d. präop. RT/CT d. lokal fortgeschrittenen Rektumkarzinoms untersuchen. In Phase I wird getestet, ob die Hinzunahme von Cetuximab zu dem etablierten RT/CT-Konzept mit Cap und Ox durchführbar ist. Aus Sicherheitsgründen wird zunächst die Dosierung des Cap auf 1000 mg/m² (d1-14, d22-35) reduziert. Cap wird in Kohorten zu 3 Pat. in insgesamt 3 Stufen (1000 mg/m², 1300 mg/m², 1650 mg/m²) eskaliert. Treten bei 2/3 oder 2/6 Pat. DLTs auf, ist die MTD erreicht. Treten in der Dosisstufe 3 keine DLTs bzw. nicht mehr als bei 1/6 DLTs auf, wird diese Dosisstufe in der Phase II verwendet. Ansonsten wird die Dosisstufe der nächstniedrigeren Cap-Dosis als empfohlene Dosis für die Phase-II-Studie verwendet. Endpunkt der Phase-II ist die Rate an kompletten Remissionen.

E.2.2

Secondary objectives of the trial

• Bestimmung der akuten und chronischen Toxizität der präoperativen Radiochemotherapie (RCT) in Verbindung mit dem Antikörper Cetuximab sowie der operativen Morbidität
• Durchführbarkeit (Compliance) der Gesamttherapie (Radiochemotherapie + Cetuximab)
• Rate an histopathologischem Downstaging
• Ermittlung der Häufigkeit sphinktererhaltender Operationsverfahren bei tiefsitzenden Tumoren
• R0-Resektionsrate
• Ermittlung der Lokalrezidivrate
• Ermittlung der Fernmetastasenrate
• Ermittlung der Überlebenszeit

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

1. Alter mindestens 18 Jahre
2. Histologisch gesichertes, fortgeschrittenes primäres Rektumkarzinom bis 16 cm von der Anokutanlinie, uT3-4 und/oder uN+ oder Mason III/IV mit oder ohne synchroner Fernmetastasierung.
3. Der immunhistochemische Nachweis der EGF-Rezeptorpositivität des Tumors ist nach neuesten Daten nicht zwingend notwendig.
4. Keine Vorbehandlung außer primärer Anus praeter-Anlage (z.B. wegen drohendem Ileus)
5. ECOG-Status < 2
6. Ausreichende Knochenmarkfunktion:
Leukozyten > 3,5 x 109/L
Neutrophile > 1,5 x 109/L
Thrombozyten > 100 x 109/L
Hämoglobin > 10 g/dl
7. Ausreichende Leberfunktion:
Bilirubin ≤ 1,5 mg/dl
SGOT, SGPT, AP, Gamma-GT < des 2-fachen des oberen Grenzwertes des Normbereichs
8. Serumkreatinin < 1,5 mg/dl, Kreatinin-Clearance > 50 ml/min
9. Patienten, die die Inhalte des Protokolls verstanden und schriftlich ihr Einverständnis zur Teilnahme erklärt haben.

E.4

Principal exclusion criteria

1. Schwangere oder stillende Frauen
2. Gebär- bzw. zeugungsfähige Menschen, die nicht zu konsequenten Verhütungsmaßnahmen während der Therapie willens oder in der Lage sind.
3. Zurückliegender oder andauernder Drogen-, Medikamenten- oder Alkoholmißbrauch
4. Frühere Chemotherapie oder Therapie mit einem EGFR-Inhibitor
5. Frühere Radiotherapie des Beckens
6. Gleichzeitige oder innerhalb von 4 Wochen liegende Teilnahme an einer anderen Studie mit einem oder mehreren in Erprobung befindlichen Medikamenten.
7. Gleichzeitige Therapie mit anderen Antitumormitteln
8. Patienten, die nicht in der Lage oder bereit sind, sich protokollgerecht zu verhalten und behandeln sowie nachuntersuchen zu lassen.
9. Patienten mit unkontrollierten schwerwiegenden, körperlichen oder geistigen Erkrankungen, wie z.B.:
- Instabile kardiale Erkrankung trotz medikamentöser Behandlung, Myokardinfarkt innerhalb der letzten 6 Monate vor Studienbeginn
- Neurologische oder psychiatrische Störungen einschließlich Demenz und Anfallsleiden
- Aktive, nicht-kontrollierbare Infektion oder Sepsis
- Aktive disseminierte intravasale Gerinnungsstörung
10. Symptomatische periphere Neuropathie NCI-CTC Grad > 2
11. Patienten mit Zweitmalignomen mit Ausnahme des Basalzellkarzinoms der Haut oder des Carcinoma in situ der Zervix, welche erfolgreich behandelt worden sind. Der Einschluss von Patienten mit anderen Tumoren, die erfolgreich behandelt wurden und innerhalb der letzten 5 Jahre nicht wieder aufgetreten sind, muss mit der Studienleitung (LKP) diskutiert werden.
12. Chronische Diarrhoe (> NCI CTC-Grad 1)
13. Chronisch entzündliche Darmerkrankungen andere Störungen, die die Medikamentenresorption beeinträchtigen. Dazu zählen das Dumping-Syndrom, Hinweise auf beschleunigte Dünndarmpassage, Hinweise auf Resorptionsstörungen nach Magen- oder Darmoperationen
14. Überempfindlichkeit gegenüber platinhaltigen Substanzen
15. Bekannte Grad 3/4 allergische Reaktion gegenüber monoklonalen Antikörpern
16. Gleichzeitige Behandlung mit Sorivudin und Analoga
17. Bekannte Defizienz der Dehydropyrimidindehydrogenase (DPD)

E.5 End points

E.5.1

Primary end point(s)

• Phase I: Definition der empfohlenen Dosis von Capecitabin in Kombination mit fixen Dosen von Oxaliplatin und Cetuximab und Radiotherapie
• Phase II: Häufigkeit histopathologisch kompletter Remissionen

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

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

Information not present in EudraCT

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)

Yes

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Therapieoptimierungsstudie

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

Yes

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.8.5

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

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

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2004-11-25.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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)

Operation, adjuvante Chemotherapie und Nachsorgeuntersuchungen nach den Empfehlungen der Dt. Krebsgesellschaft

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

2004-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2004-11-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-11-01

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