Clinical Trials Register

Summary
EudraCT Number:	2008-003003-31
Sponsor's Protocol Code Number:	EORTC 26082 – 22081
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-07-02
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2008-003003-31

A.3

Full title of the trial

Radiation therapy and concurrent plus adjuvant Temsirolimus (CCI-779) versus chemo-irradiation with Temozolomide in newly diagnosed glioblastoma without methylation of the MGMT gene promoter – a randomized multicenter, open-label, Phase II study

A.4.1

Sponsor's protocol code number

EORTC 26082 – 22081

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	EORTC Headquarters
B.1.3.4	Country	Belgium
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	EORTC
B.5.2	Functional name of contact point	EORTC Medical Department
B.5.3	Address:
B.5.3.1	Street Address	Av Mounier 83/11
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1200
B.5.3.4	Country	Belgium
B.5.4	Telephone number	3227741611
B.5.5	Fax number	3227721030
B.5.6	E-mail	eortc@eortc.be

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	TORISEL
D.2.1.1.2	Name of the Marketing Authorisation holder	Wyeth Europa Ltd
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	Concentrate 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.3.9.1	CAS number	162635043
D.3.9.3	Other descriptive name	TEMSIROLIMUS
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	anti-cancer molecularly targeted drug
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Information not present in EudraCT
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
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.3.9.1	CAS number	85622931
D.3.9.3	Other descriptive name	temozolomide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 250
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	oral alkylating agent

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

patients with newly diagnosed glioblastoma (GBM) without methylation of the DNA-repair enzyme O6-methylguanin-DNA-methyltransferase (MGMT) gene promoter

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10006153
E.1.2	Term	Brain tumor
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The study’s primary objective is to document the activity profile of CCI-779 by the evaluation of OS12 in patients with newly diagnosed glioblastoma (GBM) without methylation of the MGMT gene promoter, treated with CCI-779 before and concomitantly to RT, followed by CCI-779 maintenance therapy.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are as follows:
• Investigate safety and tolerability of the combination.
• Assess progression free survival and overall survival.
• Assess biomarkers in the tumor tissue relevant to CCI-779 and disease state, and their correlation to clinical outcome.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Present with newly diagnosed histologically proven supratentorial GBM (World Health Organization (WHO) grade IV). The histological diagnosis can be obtained either from an open brain biopsy or from a neurosurgical resection of the tumor.
• Patients must be at least 18 years of age.
• Estimated life expectancy of at least 12 weeks.

• Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or open biopsy must be available for central pathology review, MGMT status determination and exploratory analysis of PI3-K/Akt/mTOR targets (P70S6K).
• A 25 ml EDTA blood sample is also required.
• WHO-ECOG Performance Status of ≤ 2.
• Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Patients of childbearing/ reproductive potential should use highly effective method of birth control as defined by the investigator. For example those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IDUs, sexual abstinence or vasectomised partner. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on contraceptives should be addressed. Women with childbearing potential must have a negative serum pregnancy test (-HCG) ≤ 14 days prior to registration and can not be breastfeeding.
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

E.4

Principal exclusion criteria

Patients will be excluded from the study if they meet any of the following criteria:
• Have had a prior malignancy within the last 5 years (other than adequately treated carcinoma in situ of the cervix, or non-melanoma skin cancer, with no subsequent evidence of recurrence).
• Having undergone only a stereotactic biopsy (open biopsy is allowed as ensuring sufficient tumor tissue yield).
• Unable to undergo Gd MRI.
• Have had chemotherapy within the last 5 years
• Prior chemotherapy for a brain tumor
• Prior RT of the head
• Are receiving concurrent administration of any other antitumor therapy
• Are using enzyme inducing anti convulsivants (in particular carbamazepine, phenobarbital and phenytoine) and are unable to discontinue use of these agents. Or any other strong inducers or inhibitors of CYP3A4.
• Planned surgery for other diseases (for example, dental extraction)
• Placement of Gliadel® wafer at surgery
• Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. Patients with a QTc prolongation >450/470 msec (males/females) and patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded, at the investigator’s discretion.
• Known hypersensitivity to the study treatment
• Current alcohol dependence or drug abuse
• Legal incapacity or limited legal capacity
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of registration

E.5 End points

E.5.1

Primary end point(s)

Probability of Survival at 12 months (OS12)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Information not present in EudraCT

E.6.2

Prophylaxis

Information not present in EudraCT

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Information not present in EudraCT

E.6.7

Pharmacodynamic

Information not present in EudraCT

E.6.8

Bioequivalence

Information not present in EudraCT

E.6.9

Dose response

Information not present in EudraCT

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

Information not present in EudraCT

E.6.12

Pharmacoeconomic

Information not present in EudraCT

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tissue collection for MGMT promotor methylation and for banking

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

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.8.2.3.1

Comparator description

Temozolomide

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

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.1.3

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

108

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)

at the discretion of the physician

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

2009-08-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-09-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-12-16

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