Clinical Trials Register

Summary
EudraCT Number:	2006-005751-16
Sponsor's Protocol Code Number:	NN028-1642
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2006-12-28
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

2006-005751-16

A.3

Full title of the trial

An open label, dose escalation safety and tolerability trial of the combination of s.c. recombinant human IL-21 (rIL-21) and sunitinib (phase 1) followed by an open label stratified randomized 2-arm trial of rIL-21 plus sunitinib versus sunitinib alone (phase 2a) in subjects with stage IV renal cell carcinoma. Trial Phase: 1/2a

A.4.1

Sponsor's protocol code number

NN028-1642

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	Novo Nordisk A/S
B.1.3.4	Country	Denmark
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
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/226
D.3 Description of the IMP
D.3.1	Product name	rIL-21
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	716840-32-3
D.3.9.2	Current sponsor code	NN028
D.3.9.3	Other descriptive name	rIL-21
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	10
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	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	No
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.2.1.1.1	Trade name	SUTENT
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited, United Kingdom
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/268
D.3 Description of the IMP
D.3.1	Product name	SUTENT
D.3.4	Pharmaceutical form	Capsule, hard
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	sunitinib
D.3.9.3	Other descriptive name	SUTENT
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	12.5
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	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

Renal cell carcinoma stage IV

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10038414

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase 1:
To assess the safety and tolerability of increasing doses of recombinant human Interleukin-21 (rIL-21), administered s.c. in a thrice weekly regimen, in combination with sunitinib 50 mg once daily (OD) p.o. administered according to manufacturer’s instructions (“4 weeks on 2 weeks off” schedule); to determine the maximum tolerated dose (MTD) in subjects with stage IV renal cell carcinoma (RCC).
Phase 2a:
To estimate the response rate of s.c. rIL-21 and sunitinib in combination, with reference to sunitinib alone, measured according to RECIST in subjects with stage IV RCC.

E.2.2

Secondary objectives of the trial

Phase 1: to: -describe the pharmacokinetic responses in subjects treated with this regimen (rIL-21 and sunitinib).-assess if antibodies against recombinant human IL-21 are induced during therapy.-describe the pharmacodynamic responses in subjects treated with this regimen.-measure effects of this treatment regimen on tumour size according to Response Evaluation Criteria In Solid Tumours (RECIST) (if applicable).
Phase 2a: to:-compare the safety profile of the combination treatment with that of sunitinib alone in terms of frequency of adverse events (incidence and severity).-describe the pharmacokinetic response in subjects treated with these regimens at steady state (rIL-21 and sunitinib).-describe the pharmacodynamic responses in subjects treated with these regimens.-estimate progression free survival in both treatment arms.-describe Health Related Quality of Life in both treatment arms.-assess if antibodies against recombinant human IL-21 are induced during therapy with rIL-21.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
2.Histologically verified and surgically incurable stage IV RCC of clear cell type. (clear cell type only required for phase 2a)
3.18 years of age or above
4.ECOG performance status of 0 or 1. Please refer to Appendix F.
5.Life expectancy of at least 3 months
6.0-2 risk factors according to Motzer criteria (favourable or intermediate risk) (1). Please be referred to Appendix D.
7.Prior resection of the primary tumour required
8.Full recovery from surgery for stage IV disease
9.Remaining measurable disease (according to RECIST) required for phase 2a only.
Haematopoietic parameters:
10.White blood cell (WBC) higher/equal than 2.5 x 10 superscript 9/L
11.Absolute neutrophil count (ANC) higher/equal than 1.5 x 10 superscript 9/L
12.Platelet count higher/equal than 100 x 10 superscript 9/L
13.Haemoglobin higher/equal than 6.2 mmol/L
14.No signs of haemolytic anaemia
15.Serum creatinine less/equal than 177 μmol/L
Hepatic parameters:
16.Bilirubin less/equal than 1.25 x upper limit of normal (ULN)
17.AST/SGOT less/equal than 2.5 x ULN
18.LDH less/equal than 2x upper limit of normal
19.Negative serologic testing for Hepatitis B and C
20. ALT ≤ 2.5 x ULN

E.4

Principal exclusion criteria

1.Previous systemic treatment for stage IV disease
2.Rare histological subtypes of RCC (true papillary, collecting duct, sarcomatoid features) applies for phase 2a only
3.History of or active presence of auto-immune diseases (except vitiligo and treated pernicious anaemia)
4.History of any other active malignancy (except basal cell carcinoma of the skin and cervical cancer in situ) within five years prior to enrolment
5.Known chronic infectious disease including human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) related illness
6.Any significant systemic disease which according to the Investigator could compromise the safety of the subject or interfere with the trial objectives
7.Concurrent treatment with systemic corticosteroids (topical or inhaled corticosteroid treatment is permitted)
8.Known or suspected allergy to trial products or related products
9.Previous participation in this trial (re-screening is allowed when agreed with the Local Trial Manager or the International Trial Manager)
10.Pregnant, breast-feeding, or the intention of becoming pregnant or not using adequate contraceptive measures (including country-specific adequate measures, if any). In Germany adequate contraception is: implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence, or vasectomised partner. No specific requirements in the Netherlands.
11.The receipt of any investigational drug within 3 months prior to start on this trial (day 1)
12.The receipt of concomitant anti-coagulation therapy Low Molecular Weight (LMW) heparins allowed).
13.Cerebrovascular accident or transient ischemic attack within the last 12 months
14.Deep venous thrombosis or pulmonary embolism within the last 12 months
Cardiac events within the last 12 months, such as:
15.Myocardial infarction
16.Severe/unstable angina
17.Coronary/peripheral artery bypass graft
18.Symptomatic congestive heart failure (CHF)
Radiotherepy:
19. Radiotherapy within the last 4 weeks prior to start of treatment

E.5 End points

E.5.1

Primary end point(s)

Phase 1:
The primary endpoint for safety is observed toxicity to the combination of rIL-21 and sunitinib assessed using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLT and MTD will be determined according to the criteria described in Section 11.11.
Phase 2a:
The primary endpoint for tumour response will be Objective Response Rate (ORR) as determined according to RECIST. An analysis will be performed when the last subject has completed the Main Trial (Week 28). Objective responses (CR and PR) will be confirmed after additionally 4 weeks and evaluated by independent and blinded radiologists.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

stratified

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.8.4.1

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

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
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	No
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 2006-12-28.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	34
F.4.2	For a multinational trial
F.4.2.1	In the EEA	98
F.4.2.2	In the whole clinical trial	98

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

2007-03-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-02-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2008-06-30

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