Clinical Trials Register

Summary
EudraCT Number:	2013-002524-16
Sponsor's Protocol Code Number:	240562-2013-01
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-09-19
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2013-002524-16

A.3

Full title of the trial

Everolimus and temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma (G3) with a Ki67 of 20-55%

A.3.1

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

Everolimus and temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma

A.4.1

Sponsor's protocol code number

240562-2013-01

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	Dept of Oncology. Haukeland University Hospital
B.1.3.4	Country	Norway
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	Novartis
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Skåne University Hospital
B.5.2	Functional name of contact point	Dept. of Oncology
B.5.3	Address:
B.5.3.1	Street Address	Getingevägen 4
B.5.3.2	Town/ city	LUND
B.5.3.3	Post code	221 85
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+464617 75 20
B.5.5	Fax number	+464617 60 23
B.5.6	E-mail	anna.sundlov@med.lu.se

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	Temodal
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme
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.3.1	Product name	Temodal
D.3.2	Product code	ATC: L01A X03
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	equal
D.3.10.3	Concentration number	150
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.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	Afinitor
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm 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.3.1	Product name	Afinitor
D.3.2	Product code	RAD001
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	Everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	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)	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Everolimus and temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma (G3) with a Ki67 of 20-55%

E.1.1.1

Medical condition in easily understood language

Everolimus and temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 study the efficacy of everolimus combined with temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma with a Ki67 of 20-55%, measured as disease control rate (non-progressive disease) at 6 months.

E.2.2

Secondary objectives of the trial

To assess:

• Overall survival
• Progression free survival
• Objective response rate
• Response duration
• Safety profile
• Quality of life using EORTC QLQ-C30

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histology and staging disease:
•Histologically proven neuroendocrine carcinoma with a Ki67 of 20-55% by local pathology review.
•Primary gastrointestinal tumor or cancer of unknown primary when metastases are mainly GI.
•The patient cannot by surgery be rendered free from disease

General conditions:

•>18 years;
•WHO performance status 1.
•Adequate haematological function
•Adequate renal and hepatic functions:
•Written informed consent prior to inclusion must be obtained and documented according to the local regulatory requirements
•Measurable disease according to RECIST criteria v 1.1.

E.4

Principal exclusion criteria

•Prior chemotherapy for advanced/metastatic disease.
•Adjuvant chemotherapy must have ended > 6 months before inclusion.
• Patients with known hypersensitivity to temozolamide, dacarbacine, everolimus or other mTOR inhibitors.
•Female patients who are pregnant or breastfeeding or adults of reproductive potential who are not using effective birth control methods. Acceptable contraceptive methods should be used by both sexes throughout the period of study treatment and continued for at least 8 weeks after termination of treatment.
•Other anti-cancer systemic treatment within the last 8 weeks, including other experimental drugs.
•Chronic infectious or immunosuppressive disease including, but not limited to, HIV, HCV and HBV.
•Uncontrolled diabetes mellitus defined as HbA1c ≥ 8% despite adequate therapy.
•Known hypersensitivity to temozolomide or everolimus, or related compounds.
•Patients receiving chronic treatment with corticosteroids or other immunosuppressive agents.
•Other serious medical condition or illness that according to the investigator could be negatively affected by the study treatment.
•Patients with history of another primary malignancy within the last 3 years, with the exception of locally treated non-melanoma skin cancer and carcinoma in situ of the uterine cervix.
•Patients that can be expected to not be able to comply to study treatment.
•Patients using significant inducers or inhibitors of CYP3A4 or P-glycoprotein (PgP) substrates 2 weeks prior to start of study medications

E.5 End points

E.5.1

Primary end point(s)

Disease control rate (CR+PR+SD) at six months according to RECIST-criteria (version 1.1).

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline CT scans must be taken within 15 days prior to start of treatment.
First CT evaluation must be performed after 6 weeks on treatment.
Thereafter patients should be evaluated every 8th (+/- 2) week.

E.5.2

Secondary end point(s)

Objective response rates (CR+PR) according to RECIST v 1.1
Duration of response defined as time from objective response to progression of disease.
Progression-free survival defined as time from study inclusion until progression of disease or death from any cause.
Overall survival defined as time from study inclusion until death from any cause.
Toxicity according to NCI CTCAE-criteria (v 4.0).
Quality of life as measured with EORTC QLQ-C30.

E.5.2.1

Timepoint(s) of evaluation of this end point

First CT evaluation must be performed after 6 weeks on treatment.
Thereafter patients should be evaluated every 8th (+/- 2) week.

Adverse events and symptoms: Every 4th (+/- 1) week from start of treatment.

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)

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

E.8.1.1

Randomised

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

Yes

E.8.1.7.1

Other trial design description

Phase II

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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

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

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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

None

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	Nordic Neuroendocrine Tumor Group
G.4.3.4	Network Country	Norway

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-05-28

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials