Clinical Trials Register

Summary
EudraCT Number:	2007-004299-38
Sponsor's Protocol Code Number:	ESPAC-4
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:	2011-03-03
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 - BfArM

A.2

EudraCT number

2007-004299-38

A.3

Full title of the trial

European Study Group for Pancreatic Cancer - Trial 4. Combination versus single agent adjuvant chemotherapy in resectable pancreatic ductal and peri-ampullary cancers.

A.3.1

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

Comparing Gemcetabine and Capecitabine versus Gemcitabine monotherapy in chemotherapy for pancreatic cancer

A.3.2

Name or abbreviated title of the trial where available

ESPAC-4

A.4.1

Sponsor's protocol code number

ESPAC-4

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN96397434

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	The University of Liverpool
B.1.3.4	Country	United Kingdom
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	University of Liverpool
B.5.2	Functional name of contact point	Cancer Research Centre
B.5.3	Address:
B.5.3.1	Street Address	3 Brownlow Street
B.5.3.2	Town/ city	Liverpool
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	441517948932

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.2.5	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	gemcitabine
D.3.2	Product code	Gem
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	gemcitabine
D.3.9.1	CAS number	95058-81-4
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	No
D.3.11.8	Extractive medicinal product	No
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	Gemcitabine (INN) is a pyrimidine analogue.
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.2.5	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	capecitabine
D.3.2	Product code	Cap
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	capecitabine
D.3.9.1	CAS number	154361-50-9
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	No
D.3.11.8	Extractive medicinal product	No
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	non-cytotoxic fluoropyrimidine carbamate

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

Resectable pancreatic cancer

E.1.1.1

Medical condition in easily understood language

surgically removable pancreatic cancer

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10033602
E.1.2	Term	Pancreatic adenocarcinoma resectable
E.1.2	System Organ Class	100000004864

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 investigate if combination chemotherapy (gemcitabine and capecitabine), when used as adjuvant therapy in patients following resection for pancreatic adenocarcinoma, improves survival over adjuvant therapy using gemcitabine alone.

E.2.2

Secondary objectives of the trial

1. To compare the proportion of grade 3/4 toxicity across the treatment types.
2. To assess Quality of Life over time and treatment groups using the EORTC-C30 questionnaire.
3. To investigate and compare two year survival rates for the treatments.
4. To investigate and compare five year survival rates for the treatments.
5. To assess and compare relapse free survival (RFS).

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

There is an associated translational study for which, the objective is to collect and store frozen tissue, formalin fixed paraffin embedded tissue and plasma samples from patients in the trial. We shall aim to identify an expression profile in tumours associated with good or poor response to capecitabine or gemcitabine, allowing correlation with somatic and germline genetic features facilitating development of a practical molecular response signature. It is planned to undertake analysis of key enzymes and nucleoside transporters involved in gemcitabine and capecitabine metabolism and uptake (including polymorphisms).

The outcome is to identify a response profile with pancreatic cancer which will allow immediate improvement in treatment of this disease, facilitate identification of novel drug targets for patients who do not respond to present regimens and will act as a template for identification of similar profiles for other forms of cancer.

E.3

Principal inclusion criteria

1. A) Patients who have undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection)
or
B) Patients who have undergone complete macroscopic resection for peri-ampullary carcinoma (R0 or R1 resection).
2. Completion of all pre-operative investigations.
3. Histological confirmation of the primary diagnosis.
4. Histological examination of all resection margins.
5. Patients randomised ideally within 12 weeks of surgery, although case by case the CI will consider patients up to 14 weeks, and can begin treatment ideally within 14 weeks surgery
6. No evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs – CT (chest, abdomen, pelvis) scan within 3 months prior to randomisation..
7. A WHO performance status <2
8. Creatinine clearance ≥ 50ml/min (according to Cockcroft and Gault, or equivalent value following local practice).
9. Fully recovered from the operation and fit to take part in the trial.
10. Able to attend for administration of the adjuvant therapy.
11. Able to attend for long-term follow-up.
12. Life expectancy > 3 months.
13. No previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix).
14. No serious medical or psychological condition precluding adjuvant treatment.
15. Fully informed written consent given.

E.4

Principal exclusion criteria

1. Use of neo-adjuvant chemotherapy or other concomitant chemotherapy.
2. Patients with pancreatic lymphoma.
3. Macroscopically remaining tumour (R2 resection).
4. Patients with TNM Stage IV disease.
5. Patients younger than 18 years.
6. Pregnancy.
7. New York Heart Association Classification Grade III or IV.
8. Previous chemotherapy.
9. All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom.
10. Patients with known malabsorption.
11. Patients with a baseline neutrophil count of <1.5 x 109/l.
12. Patients with a baseline platelet count of <100 x 109/l.
13. Patients with severe hepatic impairment.

E.5 End points

E.5.1

Primary end point(s)

Length of survival. This measure is length of survival defined as number of days between date of randomisation and date of death due to any cause (event) or date of last follow-up if patient is still alive at time of analysis (censored).

E.5.2

Secondary end point(s)

Pancreatic Ductal Adenocarcinoma:
1. Toxicity
2. Quality of life (assessed using the EORTC QLQ-C30 v3)
3. Two year survival
4. Five year survival
5. Relapse free survival (RFS)

Peri-Ampullary Carcinoma:
1. Toxicity
2. Quality of life
3. Four year survival
4. Relapse free survival (RFS)

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

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

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

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

Information not present in EudraCT

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

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 the last follow up visit of the last patient randomised on to 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

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:

534

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

534

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 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 2011-03-03.

Yes

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

190

F.4.2

For a multinational trial

F.4.2.1

In the EEA

677

F.4.2.2

In the whole clinical trial

1068

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 will be treated with the best available medical treatment according to the specific sites SOP´s.

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

2011-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-15

P. End of Trial
P.	End of Trial Status	Completed

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