Clinical Trials Register

Summary
EudraCT Number:	2015-002685-23
Sponsor's Protocol Code Number:	ICT-107-301
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-02-24
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

Austria - BASG

A.2

EudraCT number

2015-002685-23

A.3

Full title of the trial

A Phase III randomized double-blind, controlled study of ICT-107 with maintenance temozolomide (TMZ) in newly diagnosed glioblastoma following resection and concomitant TMZ chemoradiotherapy.

A.3.1

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

Phase III (main) study of medicinal product, code ICT-107, along with standard anti-tumour therapy, temozolomide (TMZ), in patients who have newly diagnosed glioblastoma (brain tumour), after surgery along with TMZ and radiation therapy

A.3.2

Name or abbreviated title of the trial where available

STING (Study of Immunotherapy in Newly Diagnosed Glioblastoma)

A.4.1

Sponsor's protocol code number

ICT-107-301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02546102

A.5.4

Other Identifiers

Name:

IND number

Number:

BB-IND-12272

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	ImmunoCellular Therapeutics, Ltd.
B.1.3.4	Country	United States
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	ImmunoCellular Therapeutics, Ltd
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ImmunoCellular Therapeutics, Ltd
B.5.2	Functional name of contact point	ImmunoCellular Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	23622 Calabasas Road, Suite 300
B.5.3.2	Town/ city	Calabasas
B.5.3.3	Post code	91302
B.5.3.4	Country	United States
B.5.4	Telephone number	+1818246 2300
B.5.5	Fax number	+1818224 5287
B.5.6	E-mail	clintrials@imuc.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	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/3/14/1247
D.3 Description of the IMP
D.3.1	Product name	ICT-107
D.3.2	Product code	ICT-107
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	ICT-107
D.3.9.3	Other descriptive name	Peptide-loaded dendritic cells
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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	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	Temodal
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	Capsule, hard
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	TEMOZOLOMIDE
D.3.9.3	Other descriptive name	TEMOZOLOMIDE
D.3.9.4	EV Substance Code	SUB10889MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	75 to 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	No

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	Dispersion for injection
D.8.4	Route of administration of the placebo	Intradermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of newly diagnosed glioblastoma

E.1.1.1

Medical condition in easily understood language

Treatment of brain tumours that have been newly diagnosed

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	19.1
E.1.2	Level	PT
E.1.2	Classification code	10018337
E.1.2	Term	Glioblastoma multiforme
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

To determine the overall survival (OS) of subjects treated with ICT-107 and standard of care (radiotherapy (RT)and Temozolomide (TMZ)) vs. placebo control and standard of care (RT and TMZ)

E.2.2

Secondary objectives of the trial

To determine the OS of subjects with unmethylated MGMT tumours treated with ICT-107 and standard of care vs. control and standard of care.
To determine the OS of subjects with methylated MGMT tumours treated with ICT-107 and standard of care vs. control and standard of care.
To evaluate progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care.
To determine the overall safey of ICT-107 vs. control.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects or Legal Authorized Representative (LAR) (varies by region) must understand and sign the study specific informed consent
2. Subjects must be in primary remission
3. Subjects should have non-measureable disease as defined by iRANO for post surgical resection as confirmed by central radiological
assessment of the MRI with residual tumor ≤ 1 cm x 1 cm on the x and y axes, i.e. patients with tumors >1 cm2 will be excluded.
4. Subjects must be HLA-A2 positive by central lab
5. Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic
studies and chemistry and coagulation profiles must meet the following criteria:
• Hemoglobin (Hgb) > 8 g/dL
• Absolute Neutrophil Count (ANC) ≥ 1500/mm3 Platelet count ≥100,000/mm3
• Blood Urea Nitrogen (BUN) < 30 mg/dL
• Creatinine < 2 mg/dL
• Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2 x upper limit of normal (ULN)
• Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x ULN unless therapeutically warranted
6. Subjects must use effective contraceptive methods during the study and for three months following the last dose of study product, if of
reproductive age and still retain fertility potential (see Section 9.2.3.3 for definition)
7. Confirmed Initial Diagnosis of glioblastoma, including documentation of unmutated iso-citrate dehydrogenase (IDH)
8. Tissue available for MGMT methylation analysis by central laboratory
9. ≥ 18 years of age
10. WHO performance score 0-2
11. Subjects must understand and sign the informed consent.

E.4

Principal exclusion criteria

1. Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used
for prevention of severe neutropenia).
2. Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
3. Subjects with concurrent conditions that would jeopardize the safety of the subject or compliance with the protocol.
4. Subjects with a history of chronic or acute hepatitis C or B or HIV infection.
5. Subjects require or are likely to require more than a 2-week course of corticosteroids for intercurrent illness. Subjects must have completed
the course of corticosteroids at the time of apheresis to meet eligibility.
6. Subjects have any acute infection that requires specific intravenous (IV) therapy. Acute IV therapy must have been completed within seven
days prior to study enrollment.
7. Subjects with active malignancy diagnosed in the past 3 years (excepting in situ tumors)
8. Subjects known to be pregnant or nursing.
9. See Section 8.12.1 for excluded therapies.
10. Patients with hypersensitivity towards a known constituent of the study therapy, TMZ or dacarbazine
11. Patients treated with a live vaccination within the past 4 weeks.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is overall survival (OS), which will be analyzed after 387 deaths have been observed, of subjects treated with ICT-107 and standard of care (RT and TMZ) vs. placebo control and standard of care (RT and TMZ)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint is overall survival (OS), which will be analyzed after 387 deaths have been observed

E.5.2

Secondary end point(s)

To determine the OS of subjects with unmethylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care
• To determine the OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.
• To evaluate progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care
• To determine the overall safety of ICT-107 vs. control

E.5.2.1

Timepoint(s) of evaluation of this end point

Final Evaluation on all endpoints at 46 months
Secondary Endpoint:
1 and 2: OS at 6, 9, 12 months, and every 3 months after until study completion.
3: Progression-free-survival (PFS) is determined based on patient having disease progression (PD). If preliminary diagnosis of PD is made at any time, follow up in 2 months to confirm. In the first cycle tumour assessments take place week 3, then cycles 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22.
4: - Overall safety assessed during Induction Phase on day of injection (weekly for 4 weeks), every 2 weeks during Maintenance Phase (Weeks 1 and 3 during Cycles 1 – 11), monthly during Extended Maintenance Phase (Cycles 12 -23). Also at time of PD confirmation and End of Study visit. Additionally, at any other time an adverse event reported.

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

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

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.8.2.4

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

Austria

Canada

France

Germany

Italy

Netherlands

Spain

Switzerland

United Kingdom

United States

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

LVLS

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.1.2.1

Number of subjects for this age range:

434

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

108

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

159

F.4.2.2

In the whole clinical trial

542

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)

After the subject has completed participation in the trial, all future care will be determined by their treating physician. After the end of study visit, subjects will be contacted by telephone every 3 months until death; date and cause of death to be documented in the subject's CRF.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	UKCRN
G.4.3.4	Network Country	United Kingdom
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	European Organisation for Research and Treatment of Cancer (EORTC)
G.4.3.4	Network Country	Belgium
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Alliance Foundation Trials, LLC (AFT)
G.4.3.4	Network Country	United States
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Canadian Brain Tumour Consortium (CBTC)
G.4.3.4	Network Country	United States

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-08-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-06-21

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