Clinical Trials Register

Summary
EudraCT Number:	2009-012576-27
Sponsor's Protocol Code Number:	SORAMIC
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:	2009-12-17
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

2009-012576-27

A.3

Full title of the trial

Evaluation of Sorafenib in combination with local micro-therapy guided by Gd-EOB-DTPA enhanced MRI in patients with inoperable hepatocellular carcinoma

A.3.1

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

Sorafenib in combination with local micro-therapy guided by Gd-EOB-DTPA (Primovist) enhanced MRI in patients with inoperable liver cancer (SORAMIC)

A.3.2

Name or abbreviated title of the trial where available

SORAMIC

A.4.1

Sponsor's protocol code number

SORAMIC

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01126645

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	Medical Faculty, University Magdeburg
B.1.3.4	Country	Germany
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	Sirtex Medical Limited
B.4.2	Country	Australia
B.4.1	Name of organisation providing support	Bayer Pharma AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	pharmtrace klinische Entwicklung GmbH
B.5.2	Functional name of contact point	Study Lead
B.5.3	Address:
B.5.3.1	Street Address	Alt-Moabit 60
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10555
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49306322270-0
B.5.5	Fax number	+49306322270-99
B.5.6	E-mail	soramic@pharmtrace.com

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	Nexavar
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
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/3/04/207
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	SORAFENIB tosylate
D.3.9.1	CAS number	284461-73-0
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	200
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	Yes
D.3.11.13.1	Other medicinal product type	chemical
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	Primovist
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG, Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	gadoxetic acid
D.3.9.1	CAS number	135326-11-3
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/ml millimole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
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)	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	Yes
D.3.11.13.1	Other medicinal product type	contrast agent for Magnetic Resonance Imaging
D.IMP: 3
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	SIR Spheres
D.2.1.1.2	Name of the Marketing Authorisation holder	Sirtex Medical Limited
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	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrahepatic use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Yttrium-90 labeled resin microspheres (concentration of at least 0.6 GBq/ml at calibration)
D.3.10	Strength
D.3.10.1	Concentration unit	GBq/ml gigabecquerel/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	0.6
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	Yes
D.3.11.13.1	Other medicinal product type	radioactive medical device (AIMD)

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Hepatocellular carcinoma (liver-predominant disease)

E.1.1.1

Medical condition in easily understood language

cancer of the liver

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019829
E.1.2	Term	Hepatocellular carcinoma recurrent
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019828
E.1.2	Term	Hepatocellular carcinoma non-resectable
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10049010
E.1.2	Term	Carcinoma hepatocellular
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019830
E.1.2	Term	Hepatocellular carcinoma 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

1. In patients in whom local ablation therapy is appropriate (local ablation group), to determine if the sorafenib in combination with tumor ablation (collectively termed RFA) prolongs the time-to-recurrence (TTR) in comparison with RFA + placebo.

2. In patients in whom tumor ablation is NOT appropriate (palliative treatment group), to determine if the combination of yttrium-90 microspheres (SIRT) + sorafenib improves the overall survival (OS) in comparison to sorafenib alone.

3. To confirm in a 2-step procedure that Primovist-enhanced MRI is non-inferior (first step) or superior (second step) compared with contrast-enhanced multislice CT for stratification of patients to a palliative vs. local ablation treatment strategy.

E.2.2

Secondary objectives of the trial

• to assess health-related quality of life
• to compare the number of detected lesions and the diagnostic confidence in Primovist-enhanced MRI with contrast-enhanced CT
• to compare Primovist-enhanced MRI with contrast-enhanced CT regarding the detection of recurrence (patients in the local ablation group only)
• to assess the safety of the combination of RFA + sorafenib in comparison to RFA + placebo
• to assess the safety of the combination of SIR-Spheres therapy and sorafenib in comparison to sorafenib alone
• to assess in the palliative study group overall survival separately for patients with and without portal thrombosis

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age: 18-85 years
2. Hepatocellular carcinoma
3. If extrahepatic metastases: liver-dominant disease
4. Stage BCLC A, B, or C
5. Child-Pugh A, Child-Pugh B up to 7 points
6. Willing to comply with all study procedures
7. Has voluntarily given written informed consent

E.4

Principal exclusion criteria

1. If female, pregnant or breast feeding (females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study)
2. If male, not using adequate birth control measures
3. One or more of the following:
- Hemoglobin <10g/dL,
- WBC <2,500 cells/mm3,
- ANC <1,500 cells/mm3,
- platelets <50,000/mm3,
- ECOG performance status >2
4. Life expectancy <16 weeks or medically unstable
5. Pulmonary metastases
6. Patients with known GFR <30 mL/min/1.73m2
7. PT-INR/PTT >1.5 times the upper limit of normal
8. uncontrolled infections at the time of microtherapy
9. Child-Pugh score >7 points;
10. Uncontrolled ascites
11. tumor load of the whole liver >70%
12. Contraindications for study medications according to product labeling or procedures
13. Having undergone surgical procedures with resection of the sphincter of Oddi
14. Significant cardiovascular disease; e.g., myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease
15. Uncontrolled hypertension
16. Thrombotic or embolic events including transient ischemic attacks within the past 6 months (tumor-related portal vein thrombosis allowed in the palliative part of the trial)
17. History of GI bleeding within 30 days before inclusion into this study
18. History of esophageal varices bleeding which has not been controlled by effective therapy and/or therapy to prevent bleeding recurrence
19. Previous malignancy other than carcinoma in situ of the skin or the cervix uteri within 5 years prior to inclusion
20. History of organ transplant (including prior liver transplantation)
21. HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) or inflammatory bowel disease
22. Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
23. Close affiliation with the investigational site; e.g. first-degree relative of the investigator.
24. Participating in another therapeutic clinical trial or has completed study participation in another therapeutic clinical trial within 30 days of enrolment into this trial
25. Having been previously enrolled in this clinical trial

E.5 End points

E.5.1

Primary end point(s)

• TTR (local ablation group)
• Overall Survival (palliative treatment group)
• number of correct assignments to a local ablation / palliative treatment strategy (diagnostic part of the study)

E.5.1.1

Timepoint(s) of evaluation of this end point

end of trial

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

overall survival: two interim analyses are planned: at 80 and 160 deaths

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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)

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

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

randomised, double blinded for sorafenib in local ablation arm; randomised, open for palliative arm

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

contrast-enhanced computed tomography

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

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

Switzerland

Turkey

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

Last visit of the last patient

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