Clinical Trials Register

Summary
EudraCT Number:	2007-003847-66
Sponsor's Protocol Code Number:	H6Q-MC-S061
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-04-11
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

2007-003847-66

A.3

Full title of the trial

Dose Finding and Randomized, Multicenter, Placebo- Controlled, Phase 2 Study of Enzastaurin and Sunitinib versus Placebo and Sunitinib in Patients with Metastatic Renal Cell Carcinoma

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

H6Q-MC-S061

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	ELI LILLY
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	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	Enzastaurin
D.3.2	Product code	LY317615
D.3.4	Pharmaceutical form	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	Enzastaurin Hydrocloride
D.3.9.1	CAS number	170364-57-5
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	125
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 Applicabile
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 ITALIA Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Buccal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUNITINIB MALEATO
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	50
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 Applicabile

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

metastatic renal cell 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	10050018
E.1.2	Term	Renal cancer metastatic

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 compare PFS of enzastaurin plus sunitinib therapy versus placebo plus sunitinib in the first-line setting for patients with metastatic clear-cell RCC.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are: to compare the following time-to-event efficacy variables between treatment arms: ○ overall survival (OS) ○ time-to-tumor progression (TTP) to estimate duration of overall response in each treatment arm to compare the overall response rate (complete response [CR] + partial response [PR]) between treatment arms using standard RECIST criteria (as described in Protocol Attachment S061.7) to compare the rate of clinical benefit (CR + PR + stable disease [SD]) between treatment arms to assess the safety and adverse events in both treatment arms to characterize the pharmacokinetics (PK) of enzastaurin and sunitinib when administered in combination to assess biomarkers (for example, PKCβ, GSK3β, S6K, PTEN, CREB) relevant to enzastaurin and disease state, and their correlation to clinical outcome.

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

FARMACOGENETICA
FARMACOCINETICA/FARMACODINAMICA

E.3

Principal inclusion criteria

1. Patients with metastatic RCC who have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for RCC (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy) 2. Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology 3. Evidence of unidimensionally measurable disease (≥1 malignant tumor mass that can be accurately measured in at least 1 dimension ≥20 mm with conventional computed tomography (CT) or magnetic resonance imaging (MRI) scan, or ≥10 mm with spiral CT scan. (If spiral CT scan is used, minimum lesion size should be twice the reconstruction interval used. For example, if reconstruction size is 7 mm, lesion size should be ≥14 mm). CT/MRI should be performed within 4 weeks prior to study entry Note: Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. 4. Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery 5. ECOG performance status score of 0 or 1 6. Have adequate bone marrow, liver, and renal function 7. Patients must be at least 18 years of age 8.Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment, based on either a serum or urine pregnancy test. Both male and female patients of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and his or her health-care team, during the study and for 3 months following the last dose of study treatment 9. No prior malignancies for ≥5 years with the exception of cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated ≥5 years prior to study entry.

E.4

Principal exclusion criteria

1. Have received prior treatment with sunitinib or enzastaurin
2. Have history of or known brain metastases, spinal cord compression,
carcinomatous meningitis, or evidence of brain or leptomeningeal
disease on screening CT or MRI scan
3. Have history of documented central nervous system disease unrelated
to cancer; for example, uncontrolled seizures, unless adequately
treated with standard medical therapy
4.Have evidence of bleeding diathesis, NCI CTCAE Grade 3
hemorrhage <4 weeks of starting the study treatment, coagulopathy, or
thromboembolic event
5.Have uncontrolled hypertension (>150/100 mm/Hg despite optimal
medical therapy), or history of poor compliance with antihypertensive
treatment.
6. Require concomitant use of potent CYP3A4 inducer, for example,
rifampicin or potent CYP3A inhibitors, such as ketoconazole.
Note: Protocol Attachment S061.4 provides an extensive list of
CYP3A4 inhibitors or inducers.
7. Have impairment of the gastrointestinal (GI) function or GI disease
that may significantly alter the absorption of study drug.
8. Current or recent (within 10 days of first dose of study treatment) daily
use of aspirin (>325 mg/day)
9.Patients who are pregnant or breast feeding.
10. Have any condition that is unstable or which could jeopardize the
safety of the patient and his/her compliance in the study (for example,
uncontrolled diabetes mellitus, pancreatitis, acute or chronic liver
disease), and preexisting thyroid abnormality with thyroid function
that cannot be maintained in the normal range with medication.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival is defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause.

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

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

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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.8.6 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

Ultima visita dell'ultimo paziente in studio

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	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
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	20
F.4.2	For a multinational trial
F.4.2.1	In the EEA	122
F.4.2.2	In the whole clinical trial	122

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

2008-03-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-12-05

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

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