Clinical Trials Register

Summary
EudraCT Number:	2019-001562-15
Sponsor's Protocol Code Number:	CAAA601A22301
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-10-21
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

Spain - AEMPS

A.2

EudraCT number

2019-001562-15

A.3

Full title of the trial

This is a multicenter, stratified, randomized, open-label comparator-controlled, Phase III study in patients with somatostatin receptor positive, well-differentiated G2 and G3, advanced GEP NETs, diagnosed within 6 months prior to screening, comparing treatment with Lutathera (7.4GBq/200 mCi x 4 administrations every 8± 1 weeks; cumulative dose: 29.6 GBq/800mCi) plus octreotide long-acting (30 mg every 8 weeks during Lutathera treatment and every 4 weeks after last Lutathera treatment) and high dose octreotide long-acting (60 mg every 4 weeks).

Este es un estudio multicéntrico, aleatorizado, abierto, estratificado y controlado con un comparador en fase III en pacientes con TNE-GEP avanzado, bien diferenciado, de Grado 2 y Grado 3 y receptor de somatostatina positivo, diagnosticado en los 6 meses anteriores a la selección, que comparará el tratamiento con Lutathera (7,4 GBq/200 mCi x 4 administraciones cada 8±1 semanas; dosis acumulada: 29,6 GBq/800 mCi) más octreotida de acción prolongada (30 mg cada 8 semanas durante el tratamiento con Lutathera y cada 4 semanas después del último tratamiento con Lutathera) y una dosis alta de octreotida de acción prolongada (60 mg cada 4 semanas).

A.3.1

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

A phase III multi-center, randomized, open-label study to evaluate the efficacy and safety of Lutathera in combination with best supportive care octreotide long-acting (30 mg), when given as a 1st line treatment in GEP-NET patients with high proliferation rate tumors (G2 and G3), in comparison to treatment with high dose (60 mg) octreotide long-acting.

Estudio multicentro, aleatorizado y abierto en fase III para evaluar la eficacia y seguridad de Lutathera en combinación con el mejor tratamiento complementario, 30 mg de octreotida de acción prolongada, cuando se administra como tratamiento de primera línea en pacientes con TNE-GEP con un alto grado de proliferación (G2 y G3) en comparación con el tratamiento con una dosis alta (60 mg) de octreotida de acción prolongada.

A.3.2

Name or abbreviated title of the trial where available

NETTER-2

A.4.1

Sponsor's protocol code number

CAAA601A22301

A.5.4

Other Identifiers

Name:

IND No.

Number:

77219

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	Advanced Accelerator Applications SA
B.1.3.4	Country	France
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	Advanced Accelerator Applications SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Advanced Accelerator Applications International SA
B.5.2	Functional name of contact point	Juergen Fleck
B.5.3	Address:
B.5.3.1	Street Address	Rue de la Tour-de-l'Ile 4
B.5.3.2	Town/ city	Geneva
B.5.3.3	Post code	1204
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41225190700
B.5.5	Fax number	+33450993071
B.5.6	E-mail	R&D-Development-Operations@adacap.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	Yes
D.2.1.1.1	Trade name	Lutathera 370 MBq/mL solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Advanced Accelerator Applications
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/523
D.3 Description of the IMP
D.3.1	Product name	Lutathera 370 MBq/mL solution for infusion
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	LUTETIUM (177LU) OXODOTREOTIDE
D.3.9.1	CAS number	437608-50-9
D.3.9.3	Other descriptive name	177Lu-DOTA0-Tyr3-Octreotate, lutetium Lu 177 dotatate
D.3.9.4	EV Substance Code	SUB180110
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	370
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	Sandostatin® LAR® 10 mg powder and solvent for suspension for injection Sandostatin® LAR® 20 mg powder and solvent for suspension for injection Sandostatin® LAR® 30 mg powder and solvent for suspension for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Ireland Limited
D.2.1.2	Country which granted the Marketing Authorisation	Malta
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	Sandostatin® LAR® powder and solvent for suspension for injection
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Octreotide
D.3.9.1	CAS number	79517-01-4
D.3.9.3	Other descriptive name	OCTREOTIDE ACETATE
D.3.9.4	EV Substance Code	SUB03490MIG
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	10 to 30
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	Yes
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

Patients with somatostatin receptor positive, well-differentiated G2 and G3, advanced GEP NETs

Pacientes con TNE-GEP avanzado, bien diferenciado, de Grado 2 y Grado 3 y receptor de somatostatina positivo.

E.1.1.1

Medical condition in easily understood language

Patients with tumors that have a specific target (GEP NET) for treatment with Lutathera

Pacientes con tumores que tienen una diana específica (TNE-GEP) para el tratamiento con Lutathera

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	21.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10077559
E.1.2	Term	Gastroenteropancreatic neuroendocrine tumour disease
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10077560
E.1.2	Term	Gastroenteropancreatic neuroendocrine tumor disease
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 demonstrate that Lutathera is superior to active comparator in delaying the time-to-first occurrence of progression or death (PFS) as first line treatment.

Demostrar que Lutathera, como tratamiento de primera línea, es superior al comparador activo para retrasar el tiempo hasta la primera constatación de progresión (SSP) o la muerte.

E.2.2

Secondary objectives of the trial

Key secondary objectives:
-To demonstrate the superiority of Lutathera, compared to active comparator, in terms of objective response
-To demonstrate the superiority of Lutathera, compared to active comparator, in terms of time to deterioration in selected QoL items/scales.

Other Secondary Objectives:
-To evaluate the efficacy of Lutathera, compared to active comparator, in keeping the disease under control
-To evaluate the efficacy of Lutathera, compared to active comparator, in terms of duration of response
-To evaluate the safety and tolerability of Lutathera
-To evaluate the effect of Lutathera on survival

Objetivos secundarios clave:
- Demostrar la superioridad de Lutathera frente a un comparador activo en términos de respuesta objetiva
- Demostrar la superioridad de Lutathera frente a un comparador activo en términos de deterioro de una selección de elementos/escalas de calidad de vida.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Presence of metastasized or locally advanced, inoperable (curative intent) histologically proven, well differentiated Grade 2 or Grade 3 gastroenteropancreatic neuroendocrine (GEP-NET) tumor diagnosed within 6 months prior to screening.
2. Ki67 index ≥10 and ≤ 55%.
3. Patients ≥15 years of age and a body weight of >40 kg at screening.
4. Expression of somatostatin receptors on all target lesions documented by CT/MRI scans, assessed by the following somatostatin receptor imaging (SRI) modalities within 3 months prior to randomization: [68Ga]-DOTA-TOC (e.g. Somakit-TOC®) PET/CT imaging or [68Ga]-DOTA-TATE PET/CT imaging (e.g. NETSPOT®) or Somatostatin Receptor scintigraphy (SRS) with 111In-pentetreotide (Octreoscan® SPECT/CT).
5. The tumor uptake observed in the target lesions must be > normal liver uptake observed on planar imaging.
6. Karnofsky Performance Score (KPS) ≥60.
7. Presence of at least 1 measurable site of disease.
8. Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities.

1. Presencia de tumor neuroendocrino gastroenteropancreático (TNE-GEP) metastatizado o localmente avanzado, inoperable (con intención curativa), bien diferenciado, de Grado 2 o Grado 3 probado histológicamente, y diagnosticado en los 6 meses anteriores a la selección.
2. Índice Ki67 ≥10 y ≤55 %.
3. Pacientes ≥15 años de edad y con peso corporal >40 kg en la selección.
4. Expresión de receptores de la somatostatina en todas las lesiones diana documentada mediante TAC/RM y evaluada mediante las siguientes modalidades de estudios de imagen del receptor de la somatostatina (SRI) en los 3 meses anteriores a la aleatorización: estudio de imagen PET/TAC con [68Ga]-DOTA-TOC (p. ej. Somakit-TOC®), estudio de imagen PET/TAC con [68Ga]-DOTA-TATE (p. ej. NETSPOT®) o gammagrafía del receptor de la somatostatina (SRS) con 111In-pentetreotida (Octreoscan® SPECT/TAC).
5. La captación tumoral observada en las lesiones diana debe ser superior a la captación hepática normal observada en imágenes planares.
6. Puntuación funcional de Karnofsky (KPS) ≥60.
7. Presencia de como mínimo un área de enfermedad medible.
8. Pacientes que hayan proporcionado un formulario de consentimiento informado firmado para participar en el estudio, obtenido antes de iniciar cualquier actividad del protocolo.

E.4

Principal exclusion criteria

1. Creatinine clearance <40 mL/min calculated by the Cockroft Gault method.
2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x10^9/L (2000/mm^3); platelets <75x10^9/L (75x10^3/mm^3).
3. Total bilirubin >3 x ULN.
4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
5. Pregnancy or lactation.
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study and for 6 months after study drug discontinuation.
7. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.
8. Documented RECIST progression to previous treatments for the current GEP-NET at any time prior to randomization.
9. Patients for whom in the opinion of the investigator other therapeutic options (eg chemo-, targeted therapy) are considered more appropriate than the therapy offered in the study, based on patient and disease characteristics.
10. Any previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or other systemic therapies administered for more than 1 month and within 12 weeks prior to randomization in the study.
11. Any previous radioembolization, chemoembolization and radiofrequency ablation.
12. Any surgery within 12 weeks prior to randomization in the study.
13. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to screening in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to randomization in the study.
14. Uncontrolled congestive heart failure (NYHA II, III, IV). Patients with history of congestive heart failure who do not violate this exclusion criterion will undergo an evaluation of their cardiac ejection fraction prior to randomization, preferably via gated equilibrium radionuclide ventriculography. The results from an earlier assessment (not exceeding 30 days prior to randomization) may substitute the evaluation at the discretion of the Investigator, if no clinical worsening is noted. The patient’s measured cardiac ejection fraction in these patients must be >40% before randomization.
15. QTcF > 470 msec for females and QTcF > 450 msec for males or congenital long QT syndrome.
16. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
17. Hyperkaleamia >6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study enrolment.
18. Any patient receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of Lutathera, or any patient receiving treatment with SSAs (eg octreotide long-acting), which cannot be interrupted for at least 6 weeks before the administration of Lutathera, unless the tumor uptake on target lesions observed by study-permitted somatostatin receptor imaging (SRI) modalities during continued long-acting SSA treatment is greater than the liver uptake observed by planar imaging.
19. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
20. Prior external beam radiation therapy to more than 25% of the bone marrow.
21. Current spontaneous urinary incontinence.
22. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
23. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
24. Patients with known intolerance or hypersensitivity to any somatostatin analogs
25. Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days.

1. Aclaramiento de creatinina <40 ml/min calculado con el método de Cockroft Gault.
2. Concentración de Hb <5,0 mmol/l (<8,0 g/dl); leucocitos <2x10^9/l (2000/mm^3); plaquetas <75x10^9/l (75x10^3/mm^3).
3. Bilirrubina total >3 veces el LSN.
4. Albúmina sérica <3,0 g/dl, a menos que el tiempo de protrombina esté dentro del intervalo normal.
5. Embarazo o lactancia
6. No se permite participar en este estudio a las mujeres potencialmente fértiles, definidas como todas las mujeres fisiológicamente capaces de quedarse embarazadas, A MENOS que utilicen métodos anticonceptivos altamente eficaces a lo largo del estudio y durante los 6 meses siguientes a la suspensión del fármaco del estudio.
7. Terapia con radionúclidos del receptor peptídico (PRRT) en cualquier momento antes de la aleatorización en el estudio.
8. Progresión RECIST documentada con tratamientos previos para el TNE-GEP actual en cualquier momento antes de la aleatorización.
9. Pacientes para los que, en opinión del investigador y basándose en las características del paciente y de la enfermedad, se consideren más apropiadas otras opciones terapéuticas (p. ej. quimioterapia dirigida) que la terapia que se ofrece en el estudio.
10. Tratamiento previo con interferón, everolimus (inhibidores de mTOR), quimioterapia u otros tratamientos sistémicos durante más de un mes en las 12 semanas anteriores a la aleatorización en el estudio.
11. Radioembolización, quimioembolización o ablación con radiofrecuencia previa.
12. Cirugía en las 12 semanas anteriores a la aleatorización en el estudio.
13. Metástasis cerebrales conocidas, a menos que hayan sido tratadas y estabilizadas durante 24 semanas como mínimo antes de la selección del estudio. A los pacientes con antecedentes de metástasis cerebral se les deberá practicar una TAC craneal con contraste para documentar una enfermedad estable antes de la aleatorización en el estudio.
14. Insuficiencia cardiaca congestiva no controlada (NYHA II, III, IV). Los pacientes con antecedentes de insuficiencia cardiaca congestiva que no violen este criterio de exclusión se someterán a una valoración de la fracción de eyección cardiaca antes de la aleatorización, preferiblemente mediante ventriculografía radioisotópica en equilibrio sincronizada. A criterio del investigador, los resultados de una evaluación previa (no más de 30 días antes de la aleatorización) podrán sustituir la evaluación, si no se observa empeoramiento clínico. La fracción de eyección cardiaca medida de estos pacientes debe ser>40 % antes de la aleatorización.
15. QTcF >470 ms en mujeres y QTcF >450 ms en hombres o síndrome de prolongación QT congénito.
16. Diabetes mellitus no controlada, definida por un valor de glucemia en ayunas >2 veces el LSN.
17. Hiperpotasemia >6,0 mmol/l (Grado 3 CTCAE) que no se haya corregido antes de la inclusión en el estudio.
18. Cualquier paciente que reciba tratamiento con octreotida de corta acción, que no se pueda suspender durante 24 h antes y 24 h después de la administración de Lutathera, o paciente que reciba tratamiento con AS (p. ej. octreotida de acción prolongada), que no pueda suspenderse durante al menos 6 semanas antes de la administración de Lutathera, a menos que la captación tumoral de las lesiones diana observada con una modalidad de estudio de imagen del receptor de la somatostatina (SRI) permitida en el estudio durante el tratamiento continuado con un AS de acción prolongada sea superior a la captación hepática observada en las imágenes planares.
19. Pacientes con cualquier otra patología médica, psiquiátrica o quirúrgica significativa, actualmente no controlada por el tratamiento, que pueda interferir con el completado del estudio.
20. Radioterapia externa previa administrada a más del 25 % de la médula ósea.
21. Incontinencia urinaria espontánea actual.
22. Otras neoplasias malignas coexistentes conocidas, excepto el cáncer de piel no melanomatoso y el carcinoma in situ de cuello uterino, a menos que haya sido tratado de forma definitiva y se haya probado la ausencia de recurrencia durante al menos 5 años.
23. Paciente con incompatibilidad conocida a las TAC con contraste i.v. por reacción alérgica o insuficiencia renal. Si puede practicarse una RM al paciente, no se excluiría al mismo.
24. Pacientes con intolerancia o hipersensibilidad conocida a cualquier análogo de la somatostatina
25. Pacientes que hayan participado en algún estudio clínico terapéutico o hayan recibido cualquier fármaco en investigación en los 30 últimos días

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS): Time from randomization to the first line progression

Supervivencia sin progresión (SSP): tiempo desde la aleatorización hasta la fecha de la primera progresión

E.5.1.1

Timepoint(s) of evaluation of this end point

After 99 PFS events

Después de 99 acontecimientos de SSP

E.5.2

Secondary end point(s)

-ORR: rate of complete and partial responses (CR, PR)

-Time to decline (TTD) by 10 points from baseline in
the total score for health status as measured by the
EORTC QLQ-G.I.NET21 questionnaire, EORTC QLQC30 questionnaire: global health status (TTD)-diarrhea (TTD)-fatigue, (TTD)- pain (TTD).

-ORR: tasa de respuestas completas y parciales (CR, PR)

-Tiempo para disminuir (TTD) la puntuación total del estado de salud en 10 puntos desde el punto de referencia, medido por los cuestionarios EORTC QLQ-G.I.NET21, EORTC QLQC30 : estado global de salud (TTD)-diarrea (TTD)-fatiga, (TTD)- dolor (TTD)

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of treatment phase or after discontinuation

Al final de la tasa de tratamiento o después de discontinuación

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

Yes

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Sandostatin LAR Depot

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

Brazil

Canada

China

France

Germany

Italy

Korea, Republic of

Netherlands

Spain

United Kingdom

United States

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

The End of Study is after 4 years have elapsed from the randomization of the last patient.

El estudio finalizará cuando hayan transcurrido 4 años desde la aleatorización del último paciente

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

112

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

101

F.4.2.2

In the whole clinical trial

222

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)

Progressive patients randomized in the control arm will be allowed to crossover to Lutathera. At the end of treatment, all patients will be continued to be treated according to local best care practice.

A los pacientes progresivos aleatorizados en el grupo control se les permitirá cruzar a Lutathera. Después del tratamiento, todos los pacientes continuarán siendo tratados de acuerdo con las mejores prácticas locales.

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

2019-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-23

P. End of Trial
P.	End of Trial Status	Ongoing

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Orphan Designation Number:
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