Clinical Trials Register

Summary
EudraCT Number:	2012-005545-20
Sponsor's Protocol Code Number:	IJBNMDOCASTOR
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-10-20
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-005545-20

A.3

Full title of the trial

The CaStOR study
Carcinoid Tumors after failure of Somatostatin analogs: a randomized phase III of Octreotide Lutate Peptid Receptor radionuclide Therapy (PRRT) versus inteRferon α-2b

A.3.1

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

Clinical-Imaging study comparing PRRT with 177Lu-DOTATATE and Interferon alpha in terms of efficacy and toxicity in progressive, unresectable, non-pancreatic gastrointestinal neuroendocrine tumors resistant to therapy with somatostatin analogues.

A.3.2

Name or abbreviated title of the trial where available

CASTOR

A.4.1

Sponsor's protocol code number

IJBNMDOCASTOR

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01860742

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	Institut Jules Bordet
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	Institut Jules Bordet
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut Jules Bordet
B.5.2	Functional name of contact point	Ioannis Karfis
B.5.3	Address:
B.5.3.1	Street Address	121 Boulevard de Waterloo
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3225413178
B.5.6	E-mail	ioannis.karfis@bordet.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	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	177Lu-DOTATATE
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	No proposed INN
D.3.9.2	Current sponsor code	IJB 177Lu_DOTATATE_IJB
D.3.9.3	Other descriptive name	LUTETIUM(177LU)-DOTA-(TYR3)-OCTREOTATE
D.3.9.4	EV Substance Code	SUB177319
D.3.10	Strength
D.3.10.1	Concentration unit	GBq gigabecquerel(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	7.2 to 7.6
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	Yes
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	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	Yes
D.2.1.1.1	Trade name	INTRON A
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme 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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	interferon alfa-2b
D.3.9.2	Current sponsor code	Interferon alfa-2b_60MIU_IJB
D.3.9.3	Other descriptive name	INTERFERON ALFA-2B
D.3.9.4	EV Substance Code	SUB12521MIG
D.3.10	Strength
D.3.10.1	Concentration unit	million IU million international units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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)	Yes
	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: 3
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	Yes
D.2.1.1.1	Trade name	INTRON A
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme 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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	interferon alfa-2b
D.3.9.2	Current sponsor code	Interferon alfa-2b_30MIU_IJB
D.3.9.3	Other descriptive name	INTERFERON ALFA-2B
D.3.9.4	EV Substance Code	SUB12521MIG
D.3.10	Strength
D.3.10.1	Concentration unit	million IU million international units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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)	Yes
	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: 4
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	Yes
D.2.1.1.1	Trade name	INTRON A
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme 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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	interferon alfa-2b
D.3.9.2	Current sponsor code	Interferon alfa-2b_18MIU_IJB
D.3.9.3	Other descriptive name	INTERFERON ALFA-2B
D.3.9.4	EV Substance Code	SUB12521MIG
D.3.10	Strength
D.3.10.1	Concentration unit	million IU million international units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	18
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)	Yes
	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

Progressive, unresectable, non-pancreatic gastrointestinal neuroendocrine tumors resistant to therapy with somatostatin analogues.

E.1.1.1

Medical condition in easily understood language

Progessive and not responding to somatostatin analogue therapy gastrointestinal (non-pancreatic) neuroendocrine tumors, not amenable to surgery with curative intent.

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10052399
E.1.2	Term	Neuroendocrine tumour
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 assess the benefit of 177Lu-DOTATATE versus interferon α-2b in patients with progressive, unresectable, non-pancreatic gastrointestinal neuroendocrine tumors, resistant to therapy with somatostatin analogues, in terms of disease control.

E.2.2

Secondary objectives of the trial

To assess efficacy and safety parameters of both treatment arms and the predictive value of tumor 68Ga-DOTATATE PET/CT and 18FDG PET/CT uptake at baseline, at mid (+/- 16th week) and end (+/- 32th week) of treatment in both arms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult patients (≥ 18 yrs).
2. Histology-proven non-pancreatic gastrointestinal NETs.
3. Disease progression under SSAs (SSAs-resistant disease). Disease progression must be documented with at least one of the following:
- Radiological disease progression (according to RECIST 1.1) on an MRI or CT over the last 12 months.
- Disease progression on a somatostatin receptor-imaging (PET/CT or SPECT/CT) over the last 12 months (apparition of new lesion(s) or increase in the transaxial plane diameter of more than 30% on the same imaging modality).
4. There should be at least one target lesion. A target lesion should fulfill all the following criteria:
- Uptake higher than the physiological liver uptake on the baseline 68Ga-DOTATATE PET/CT
- longest transaxial plane diameter ≥ 20mm measured on the CT or MRI;
- not previously irradiated.
5. Long-acting SSAs must be discontinued at least 4 weeks before the study treatment start date and, if needed, switched to short-acting analogues which must be stopped 48h before the treatment date.
6. Adequate renal function with GFR ≥ 50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test).
7. Adequate bone marrow function with:
- Hemoglobin ≥ 9 g/dL;
- Neutrophil ≥ 1.5·109/L;
- Platelet count ≥ 100·109/L.
8. Adequate liver function with:
- Total Bilirubin ≤ 2xULN;
- Transaminases (AST and ALT) ≤ 5xULN;
- Serum albumin > 3.0 g/dL with normal prothrombin time (>70%) unless for patients under coumarin anticoagulation therapy.
9. ECOG Performance Status ≤ 1.
10. Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective form of contraception for the duration of study participation and up to six months after the end of the treatment. A pregnancy test (serum) must be performed within 2 weeks prior to inclusion for every female patient of childbearing potential and it must be negative.
11. Patient’s written informed consent obtained prior to any study specific procedure.
12. All necessary baseline procedures should be performed within 2 weeks prior to randomization date.

E.4

Principal exclusion criteria

1. Resectable tumor with curative intent.
2. Any major surgery within the last 6 weeks prior to inclusion in the study.
3. Radiotherapy, chemotherapy, embolization, mammalian target of rapamycin (mTOR)-inhibitors, receptor tyrosine-kinase inhibitors or other investigational therapy within 12 weeks prior to inclusion in the study.
4. Previous PRRT or MIBG treatment.
5. Treatment with interferon 12 months prior to inclusion in the study.
6. Presence of non-benign 18FDG-positive lesions (higher than 2 x normal liver (or thoracic aorta uptake –SUVmax- in case of liver involvement)) without significant 68Ga-DOTATATE uptake.
7. Uncontrolled congestive heart failure (NYHA stade ≥ 2).
8. Diffuse bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT confirmed by MRI.
9. Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow.
10. Patients with known uncontrolled brain metastases.
11. History of other active malignant disease or clinical remission less than 5 years (except in case of non melanoma skin cancer or in situ cervical carcinoma).
12. Known autoimmune hepatitis.
13. Patients after organ transplantation under immunosuppressive therapy.
14. Patients with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator’s opinion, may interfere with completion of the study.
15. Hypersensitivity to interferon α-2b or to any component of the product.
16. Pregnant or lactating patients.

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS) defined by the time between treatment initiation and the first of the following events:
- Disease progression according to RECIST 1.1;
- Death of the patient from any cause;
- Appearance of confirmed new lesion(s) on 68Ga-DOTATATE PET/CT or 18FDG PET/CT.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every eight weeks (+/- one week) in both arms.

E.5.2

Secondary end point(s)

- Treatment response according to RECIST 1.1;
- Adverse events according to NCI- CTCAE v4.03;
- Tumor 18FDG PET/CT and 68Ga-DOTATATE PET/CT uptake at the aforementioned timepoints.

E.5.2.1

Timepoint(s) of evaluation of this end point

Every eight weeks (+/- one week) in both arms.

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

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

End of study will be declared when all the following criteria will have been met:
- After last visit of the last patient
- Safety reporting has been done for all patients
- The study is mature for the analysis of the primary endpoints as defined in the protocol, if the study reaches its primary endpoints
- The database has been fully cleaned and frozen for all analyses.

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

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.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)

Best medical routine care at the discretion of the physiian according to standard local practices

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

2014-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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