Clinical Trials Register

Summary
EudraCT Number:	2009-014440-10
Sponsor's Protocol Code Number:	EMR200068-006
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-10-23
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

UK - MHRA

A.2

EudraCT number

2009-014440-10

A.3

Full title of the trial

A Phase II, Open-label, 1:1 Randomized, Controlled Trial Exploring the Efficacy of EMD 1201081 in Combination with Cetuximab in Second-Line Cetuximab-Naïve Subjects with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

A.3.1

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

Clinical trial investigating EMD 1201081 in Combination with Cetuximab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

A.3.2

Name or abbreviated title of the trial where available

EMD 1201081 in Cetuximab-Naïve Subjects with R/M SCCHN

A.4.1

Sponsor's protocol code number

EMR200068-006

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	Merck KGaA
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	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	Merck KGaA
B.5.2	Functional name of contact point	Communication Center Marck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Str. 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	496151725200
B.5.5	Fax number	496151722000
B.5.6	E-mail	service@merck.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	No
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	EMD 1201081
D.3.2	Product code	EMD 1201081
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	EMD 1201081
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
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	Erbitux 5 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck KGaA
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	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	205923564
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	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.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

Recurrent/metastatic squamous cell cancer of the head and neck

E.1.1.1

Medical condition in easily understood language

Recurrent/metastatic squamous cell cancer of the head and neck

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	LLT
E.1.2	Classification code	10060121
E.1.2	Term	Squamous cell carcinoma of head and neck
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 evaluate progression-free survival time of subjects treated with EMD 1201081 + cetuximab compared to cetuximab alone in cetuximab-naïve subjects with recurrent and/or metastatic SCCHN who have progressed on a cytotoxic therapy.

E.2.2

Secondary objectives of the trial

• To evaluate the overall response (by RECIST 1.0) or disease control status (CR + PR + SD) of subjects treated with EMD 1201081 + cetuximab compared to cetuximab alone in subjects with R/M SCCHN.
• To evaluate overall survival time in subjects treated with EMD 1201081 + cetuximab as second-line treatment.
• To study the safety and tolerability of the combination EMD 1201081 + cetuximab in the overall trial population.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed and dated written informed consent prior to any trial-specific procedure.
2. Male or female, age ≥ 18 years.
3. Histologically confirmed squamous cell carcinoma of the head and neck that is recurrent and/or metastatic; documented in the medical record.
4. History of progressing disease on a first-line cytotoxic chemotherapy regimen such as 5-FU + cisplatin, taxanes, etc. for their R/M SCCHN. (A history of chemotherapy/ radiation therapy for localized disease does not count as a first-line regimen.)
5. The subject is suited for systemic therapy in the opinion of the Investigator.
6. At least one radiographically documented lesion assessable according to RECIST 1.0. Lesions in previously irradiated areas should be measurable (i.e. the lesion must be adequately measurable in at least one dimension; longest diameter to be recorded as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan). If the sole site of measurable disease is in a prior radiation field, there must be unequivocal evidence of progression at ≥ 8 weeks since the completion of radiation or a positive biopsy.
7. ECOG performance status of 0 or 1.
8. If female, either post-menopausal, surgically sterile, or having a negative urine or serum pregnancy test (β-HCG) at screening and practicing medically accepted contraception. If male, practicing contraception if risk of conception exists. For relevant subjects, the duration of contraception should be 1 week prior to the start of therapy through 4 weeks after receipt of trial therapy.
9. Recovered from previous toxicities of prior cytotoxic regimen to CTCAE Grade 1 (with the exception of alopecia).
10. Hemoglobin ≥ 9 g/dL (without transfusion support, no transfusion within 7 days of screening).
11. Neutrophils ≥ 1.5 x 109/L.
12. Platelets ≥ 100 x 109/L.
13. PT/PTT ≤ 1.5 times the upper limit of normal for the site, unless there is therapeutic anti-coagulation (see below; INR values should be converted to PT for screening).
14. Serum creatinine ≤ 1.5 times the upper limit of normal for the site.
15. ALT and AST ≤ 3 times the upper limit of normal for the site.
16. Be willing and able to comply with the protocol procedures for the duration of the trial.

E.4

Principal exclusion criteria

1. History of prior exposure to cetuximab or panitumumab or any other approved or investigational anti-EGFR agents.
2. Undifferentiated nasopharyngeal carcinoma.
3. Chemotherapy, radiotherapy or any investigational agents within 4 weeks of first dose of trial medication.
4. Major surgical or planned procedure within 30 days prior to first dose of trial medication (isolated biopsies are not counted as major surgical procedures).
5. Other active malignancy besides non-metastatic basal cell or squamous cell carcinoma of the skin or second primary squamous cell carcinoma
of the head and neck.
6. Impaired cardiac function (e.g. left ventricular ejection fraction < 45% defined by
echocardiograph or other study), history of uncontrolled serious arrhythmia, unstable
angina pectoris, congestive heart failure NYHA III and IV), myocardial infarction within
the last 12 months prior to trial entry, signs of pericardial effusion.
7. Hypertension uncontrolled by standard pharmacologic therapies.
8. History of diagnosed interstitial lung disease.
9. Patient requires systemic anti-coagulation (e.g. warfarin > 10 mg/day).
10. Pregnancy or breast feeding.
11. Legal incapacity or limited legal capacity.
12. Significant medical or psychiatric disease which makes the trial inappropriate for the subject in the Investigator’s opinion.
13. Any brain metastasis and/or leptomeningeal disease (known or suspected).
14. Significant pre-existing immune deficiency such as infection by HIV (documented or known).
15. Clinically significant ongoing infection.
16. Known hypersensitivity to the trial treatments.
17. Participation in another clinical trial within the past 30 days.
18. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
19. Other significant disease that in the Investigator’s opinion would exclude the subject from the trial.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS) time

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation will be performed at baseline and every 6 weeks after randomization/start of treatment

E.5.2

Secondary end point(s)

To evaluate the overall response (by RECIST 1.0) or disease control status (CR + PR + SD) of subjects treated with EMD 1201081 + cetuximab compared to cetuximab alone in subjects with R/M SCCHN.

E.5.2.1

Timepoint(s) of evaluation of this end point

The best overall response will be derived from the assessments of overall response at the individual time points

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

Yes

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

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Croatia

Czech Republic

France

Hungary

Lithuania

Poland

Slovakia

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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 end of the trial is defined as 1 year after the last subject has had his/her End-of-Study Visit.

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