Clinical Trials Register

Summary
EudraCT Number:	2007-006637-14
Sponsor's Protocol Code Number:	A6181170
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2008-12-10
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-006637-14

A.3

Full title of the trial

A MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY OF
SUNITINIB MALATE VERSUS BEST LOCALLY AVAILABLE CARE IN
PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

A6181170

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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	PFIZER
B.1.3.4	Country	Italy
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	Yes
D.2.1.1.1	Trade name	Sutent
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	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.3.9.1	CAS number	341031-54-7
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	Yes
D.3.11.13.1	Other medicinal product type	Di natura chimica
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
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	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.3.9.1	CAS number	341031-54-7
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	25
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	Di natura chimica

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

Advanced Hepatocellular Carcinoma

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10049010
E.1.2	Term	Carcinoma hepatocellular

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 demonstrate improved overall survival on sunitinib as compared to best locally
available care in patients with advanced hepatocellular carcinoma

E.2.2

Secondary objectives of the trial

To compare progression-free survival and time to tumor progression between both
treatment arms
To evaluate the safety and tolerability of sunitinib in this patient population
To compare patients’ health status between both treatment arms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically-confirmed diagnosis of hepatocellular carcinoma that is locally advanced
or metastatic (histological diagnosis obtained from a prior tumor biopsy specimen is
acceptable).
2. Measurable disease according to RECIST. At least one target lesion should not have
previously received any local therapy, such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radio-frequency ablation, percutaneous
ethanol injection or cryoablation, unless it has subsequently progressed according to
RECIST.
3. Resolution of all acute toxic effects of any prior local treatment to National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
grade </=1.
4. Child-Pugh class A (for the determination of the Child-Pugh class, use the table reported
in Appendix 5).
5. Eighteen years of age or older.
6. ECOG performance status 0 or 1.
7. Required baseline laboratory data within the following parameters:
Neutrophils >/= 1,500/uL
Platelets >/= 75,000/uL
Hemoglobin >/= 9.0 g/dL
Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT])
and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase
[SGPT]) </= 5 x ULN
Serum creatinine </= 1.5 x ULN
INR <1.7 or prothrombin time (PT) < 4 seconds above ULN
Serum albumin > 3.5 g/dL (* >7= 2.8 g/dL)
Total bilirubin < 2 mg/dL (* </= 3 mg/dL)
* ONLY ONE of these 2 last criteria may have a score of 2 according to the Child-Pugh
scoring system.
8. Candidate for treatment with one of the regimens listed if patient is randomized to the
control arm. Safety precautions standard for specific regimens but not stated in study
entry criteria must be ensured by the investigator prior to randomization. Examples
include precautions for some chemotherapy regimens based on moderately elevated liver
function tests and prior hypersensitivity to an agent.
9. Signed and dated informed consent indicating that the patient (or legally acceptable
representative) has been informed of all the pertinent aspects of the trial prior to
enrollment.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures, including completion of patient-reported outcome (PRO)
questionnaires.

E.4

Principal exclusion criteria

1. Prior systemic treatment for HCC, including prior treatment with sunitinib or another
investigational agent.
2. Any prior local therapy (such as surgery, radiation therapy, hepatic arterial embolization,
TACE, hepatic arterial infusion, radiofrequency ablation, percutaneous ethanol injection
or cryoablation) within 4 weeks of study entry.
3. Prior history of liver transplant.
4. Presence of clinically relevant ascites (e.g., requiring therapeutic paracentesis or that can
be classified as Child-Pugh score >/= 2).
5. NCI CTCAE grade >/= 3 hemorrhage within 4 weeks of starting study treatment, or
documented variceal hemorrhage of any grade within 12 months of study entry (as documented by endoscopy).
6. Presence of esophageal varices at risk of bleeding and/or serious or non-healing
wound/ulcer (as documented by endoscopy).
7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 28 days of study entry.
8. Any of the following within the 12 months prior to study drug administration:
severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic
congestive heart failure, cerebrovascular accident, including transient ischemic attack, or
pulmonary embolism.
9. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma,
squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been
adequately treated without evidence of recurrent disease for 12 months.
10. History of or known brain metastases, spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease.
11. Ongoing cardiac dysrhythmias of NCI CTCAE grade >/= 2, atrial fibrillation of any grade,
or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females.
12. Hypertension that cannot be controlled by medications (blood pressure >150/100 mm Hg
despite optimal medical therapy).
13. Treatment with potent CYP3A4 inhibitor within 7 days of study entry or with potent
CYP3A4 inducer within 12 days of study entry.
14. Concomitant treatment with botanical formulation having an approved indication for
cancer treatment, such as “Xiao Chai Hu Tang”, “Kanglaite”, etc.
15. Ongoing treatment with therapeutic levels of coumarin derivatives or oral anti-vitamin K agents.
16. Inability to swallow oral medications, or presence of active inflammatory bowel disease,
partial or complete bowel obstruction or chronic diarrhea.
17. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness.
18. Pregnancy or breastfeeding. All female patients with reproductive potential must have a
negative pregnancy test (serum or urine) within the 7 days prior to study enrollment.
19. Fertile patients unwilling or unable to use adequate contraception, as defined in Life Style
Guidelines, Section 4.4, to prevent pregnancy during the study.
20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
that may increase the risk associated with study participation or study drug
administration, or may interfere with the interpretation of study results, and in the
judgment of the investigator would make the patient inappropriate for entry into this study.

E.5 End points

E.5.1

Primary end point(s)

Overall Survival (OS)

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

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

Yes

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.8.4.1

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

150

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

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	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	No
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	15
F.4.2	For a multinational trial
F.4.2.1	In the EEA	136
F.4.2.2	In the whole clinical trial	680

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

2008-09-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-04-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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