Clinical Trials Register

Summary
EudraCT Number:	2012-001879-37
Sponsor's Protocol Code Number:	ArtscanIII
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-19
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

2012-001879-37

A.3

Full title of the trial

A randomized multicenter phase III study of cisplatin plus radiotherapy compared to cetuximab plus radiotherapy in locally advanced head and neck cancer

A.3.1

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

A randomized study of cisplatin plus radiotherapy compared to cetuximab plus radiotherapy in locally advanced head and neck cancer

A.3.2

Name or abbreviated title of the trial where available

ARTSCANIII

A.4.1

Sponsor's protocol code number

ArtscanIII

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	Department of Oncology, Skåne University Hospital Lund
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	Cancerfonden
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	Maria Gebre-Medhin
B.5.2	Functional name of contact point	Coordinating investigator
B.5.3	Address:
B.5.3.1	Street Address	Department of Oncology, Skåne University Hospital Lund
B.5.3.2	Town/ city	Lund
B.5.3.3	Post code	Se-211 85
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+464617 00 00
B.5.6	E-mail	maria.gebre-medhin@skane.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	Erbitux
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CETUXIMAB
D.3.9.1	CAS number	205923-56-4
D.3.9.4	EV Substance Code	SUB01178MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	No
D.3.11.9	Recombinant medicinal product	Yes
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	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	Cisplatin
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CISPLATIN
D.3.9.1	CAS number	15663-27-1
D.3.9.4	EV Substance Code	SUB07483MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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

Stage III and IV head and neck squamous cell cancer (HNSCC) without radiographic signs of distant metastases aimed for radiotherapy with curative intent

E.1.1.1

Medical condition in easily understood language

Stage III and IV head and neck squamous cell cancer (HNSCC) without radiographic signs of distant metastases aimed for radiotherapy with curative intent

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10071536
E.1.2	Term	Head and neck cancer stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10071537
E.1.2	Term	Head and neck cancer stage III
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 study whether overall survival is improved by treatment with radiotherapy + cetuximab compared to treatment with radio radiotherapy + cisplatin in the treatment of patients with locally advanced (stage III-IV) head and neck squamous cell carcinoma (HNSCC).

E.2.2

Secondary objectives of the trial

•To study whether local control is enhanced with dose-escalated radiotherapy + cetuximab/cisplatin compared to treatment with standard-dose radiotherapy + cetuximab/cisplatin in locally advanced (T3 and T4) tumours
•To describe early and late side effects of the treatment arms
•To compare local and regional tumour control between the treatment arms
•To determine pattern of failure
•To evaluate quality of life
•To determine if HPV and p16 positivity can consist a prognostic marker
•To compare normal tissue sparing and normal tissue complications with different treatment techniques (3D-CRT vs. IMRT/VMAT/HTT) and radiotherapy only vs. radiochemotherapy by comparison with the results from the first ARTSCAN study
•To make a health economic comparison between treatment with radiotherapy and cisplatin and treatment with radiotherapy and cetuximab
•To find biomarkers that can guide therapy decisions

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

The study has a separate translational part, with investigation of blood cells as well as tumour tissue, in order to study prognostic and predictive biomarkers. This part requires a separate informed consent.

E.3

Principal inclusion criteria

1.The patient must be over 18 years old.
2.Histologically or cytologically confirmed HNSCC of the oropharynx, hypopharynx, larynx or of the oral cavity aimed for unimodal treatment with radiotherapy with curative intent.
3.Tumour stage III and IV according to the UICC TNM classification, but with no evidence of distant metastases beyond the regional nodes in the neck.
4.WHO/ECOG performance status 0-2
5.The patient must be expected to withstand radiotherapy combined with cisplatin or cetuximab.
6.The patient must be able to understand the information about the treatment and give a written informed consent to participate in the trial.
7.Adequate follow-up study must be possible; this will exclude a patient who is uncooperative.
8.Adequate renal function, creatinine clearance > 50 mL/min/1.73 estimated according to local practise at each study centre

E.4

Principal exclusion criteria

1.Previous malignant disease in the head and neck region, with exception for basal cell carcinoma or curatively treated squamous cell carcinoma of the skin with follow-up time of at least 3 years.

2.Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix uteri, or other previous malignancy with a disease-free interval of at least 5 years.

3.Two or more synchronous primary HNSCC at time of diagnosis

4.Co-existing disease prejudicing survival (expected survival >6 months).

5.Absolute neutrophil count (ANC) < 1.5 x 109/L.

6. Platelet count < 100 x 109/L.

7. Bilirubin > 1.5 times upper limit of normal (ULN)

8. Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) >3 times ULN

9. Pregnancy or lactation

10. Allergy to study drug or to the excipients in their formulation.

11. Peripheral neuropathy > grade 2 according to CTCAE v4.0, grade 2 = moderate symptoms limiting instrumental ADL)

12. Hearing loss / tinnitus is a relative exclusion criteria;

13. Severe cardiac illness

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS).

E.5.1.1

Timepoint(s) of evaluation of this end point

Follow up by the protocol ends at five years after end of treatment

E.5.2

Secondary end point(s)

•Differences in local control between treatment with dose-escalated radiotherapy + cetuximab/cisplatin compared to treatment with standard-dose radiotherapy + cetuximab/cisplatin in locally advanced (T3 and T4) tumours
•Early and late side effects
•Local and regional tumour control
•Pattern of failure
•Quality of life
•Prognostic value of HPV and p16 positivity
•Normal tissue sparing and normal tissue complications
•Cost-utility analysis
•Exploratory, biomarker investigations (separate informed consent required)

E.5.2.1

Timepoint(s) of evaluation of this end point

Five years after end of treatment

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)

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Two different doses of radiotherapy

E.8.2.4

Number of treatment arms in the trial

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

The last patients last vist

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

E.8.9.2

In all countries concerned by the trial 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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

218

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

Yes

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

618

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

618

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 according to clinical routines

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

2013-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2024-01-10

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