Clinical Trials Register

Summary
EudraCT Number:	2020-001970-31
Sponsor's Protocol Code Number:	HYBRID_ENDONODE
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-06-22
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

2020-001970-31

A.3

Full title of the trial

Sentinel node in endometrial cancer using hybrid detection ([99mTc] Tc-albumin nanocoloid-ICG). Comparative pilot study between the lymphatic map derived from the cervical versus myometrial puncture.

Ganglio centinela en el cáncer de endometrio mediante detección híbrida ([99mTc]Tc-nanocoloide de albúmina-ICG). Estudio piloto comparativo entre el mapa linfático derivado de la punción cervical versus miometrial.

A.3.1

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

Detection of the sentinel lymph node in endometrial cancer by hybrid tracer [99mTc] Tc-albumin nanocoloid-ICG

Detección del ganglio centinela en cáncer de endometrio mediante trazador híbrido [99mTc]Tc-nanocoloide de albúmina-ICG

A.4.1

Sponsor's protocol code number

HYBRID_ENDONODE

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	Fundació Clínic per a la Recerca Biomèdica
B.1.3.4	Country	Spain
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	ISCIII
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital Clínic. Servicio de Medicina Nuclear
B.5.2	Functional name of contact point	Pilar Paredes
B.5.3	Address:
B.5.3.1	Street Address	Villarroel, 170
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34932275400
B.5.5	Fax number	+34032279877
B.5.6	E-mail	pparedes@clinic.cat

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	[99mTc]Tc-nanocoloide de albúmina-ICG
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Endocervical use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	human albumin nanocolloids
D.3.9.3	Other descriptive name	TECHNETIUM (99MTC) HUMAN ALBUMIN INJECTION
D.3.9.4	EV Substance Code	SUB129903
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	indocyanine green
D.3.9.1	CAS number	3599-32-4
D.3.9.3	Other descriptive name	INDOCYANINE GREEN
D.3.9.4	EV Substance Code	SUB14208MIG
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)	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	Rotop
D.2.1.1.2	Name of the Marketing Authorisation holder	Rotop Pharmaka AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	albumin [99mTc]Tc-nanocolloid
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Endocervical use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	human albumin nanocolloids
D.3.9.3	Other descriptive name	TECHNETIUM (99MTC) HUMAN ALBUMIN INJECTION
D.3.9.4	EV Substance Code	SUB129903
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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.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 endometrial cancer who are going to undergo surgery for the primary tumor and lymph node study using lymphadenectomy and detection of the sentinel node

Patients with endometrial cancer who are going to undergo surgery

E.1.1.1

Medical condition in easily understood language

Endometrial cancer patients undergoing surgery

Pacientes con cáncer de endometrio que vayan a ser sometidas a cirugía

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	10014733
E.1.2	Term	Endometrial cancer
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To estimate the ratio of intraoperative sentinel node detection in endometrial cancer using the hybrid detection of RT and ICG ([99mTc] Tc-albumin nanocoloid-ICG)

Estimar la proporción de detección intraoperatoria del ganglio centinela en el cáncer de endometrio utilizando la detección híbrida de RT e ICG ([99mTc]Tc-nanocoloide de albúmina-ICG).

E.2.2

Secondary objectives of the trial

1. To evaluate if the proportion of intraoperative detection of the sentinel node (GC) in endometrial cancer using the detection of the hybrid radiotracer [99mTc] Tc-albumin nanocoloid-ICG (hybrid RT) is higher than that obtained by injecting only the radiotracer [99mTc] Tc-albumin nanocoloid (RT).
2. To estimate the diagnostic capacity parameters of hybrid RT detection by transvaginal ultrasound-guided myometrial injection (TUMIR).
3. To compare the lymphatic map obtained by detection of the hybrid RT or by exclusive detection with RT according to the cervical injection route or the TUMIR.
4. Incidence of hypersensitivity reactions and adverse events related to tracer injection (hybrid RT and RT)

1. Evaluar si la proporción de detección intraoperatoria del GC en el cáncer de endometrio utilizando la detección del Radiotrazador híbrido [99mTc]Tc-nanocoloide de albúmina-ICG (RT híbrido) es superior a la obtenida al inyectar por la misma vía únicamente el radiotrazador [99mTc]Tc-nanocoloide de albúmina (RT).
2. Estimar los parámetros de capacidad diagnóstica de la detección del RT híbrido mediante la inyección miometrial guiada por ecografía transvaginal (TUMIR).
3. Comparar el mapa linfático obtenido mediante detección del RT híbrido o mediante detección exclusiva con RT según la vía de inyección cervical o la TUMIR.
4. Incidencia de reacciones de hipersensibilidad y acontecimientos adversos relacionados con la inyección de los trazadores

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 years.
2. Histological diagnosis of endometrial cancer with high risk criteria according to the following criteria:
- unfavorable histology according to FIGO (serous adenocarcinoma, clear cell or carcinosarcoma)
- nuclear grade 3
- suspected myometrial invasion> 50% by magnetic resonance imaging (MRI) or transvaginal ultrasound
3. Women of childbearing age must have a transvaginal ultrasound that rules out pregnancy and must commit to using highly effective contraceptive methods (vasectomized partner and sexual abstinence) until the hysterectomy is performed.
4. Patient who gives written informed consent.

1. Edad ≥ 18 años.
2. Diagnóstico histológico de cáncer de endometrio con criterios de alto riesgo según los siguientes criterios:
- histología desfavorable según la FIGO (adenocarcinoma seroso, de células claras o carcinosarcoma)
- grado nuclear 3
- sospecha de invasión miometrial >50% por resonancia magnética (RM) o ecografía transvaginal
3. Las mujeres en edad fértil* deben tener una ecografía transvaginal que descarte embarazo y deben comprometerse a utilizar métodos anticonceptivos altamente eficaces (pareja vasectomizada y abstinencia sexual) hasta la realización de la histerectomía.
4. Paciente que otorgue el consentimiento informado por escrito.

E.4

Principal exclusion criteria

1. Pregnancy or lactation.
2. Suspected lymph node or distant metastatic disease in the preoperative study.
3. History of previous surgery or radiotherapy in the areas of pelvic and paraortic lymph node drainage or lymph node involvement of any other etiology.
4. Body mass index (BMI) greater than 45 Kg / m2.
5. Patients who, in the judgment of the investigator, are not eligible to participate, regardless of reason, including medical or clinical conditions, or participants potentially at risk of not complying with the study procedures.
6. Known hypersensitivity to some of the active substances or excipients of RT or ICG (including previous history of hypersensitivity to products containing human albumin).
7. Hypersensitivity to sodium iodide.
8. Patients allergic to iodine.
9. Patients with clinical hyperthyroidism, autonomous thyroid adenomas, and diffuse focal and autonomic abnormalities of the thyroid gland.

1. Embarazo o lactancia.
2. Sospecha de enfermedad metastásica ganglionar o a distancia en el estudio preoperatorio.
3. Antecedente de cirugía o radioterapia previa en las áreas de drenaje ganglionar pelvianas y paraórticas o afectación ganglionar de cualquier otra etiología.
4. Índice de masa corporal (IMC) superior a 45 Kg/m2.
5. Pacientes que, a criterio del investigador, no sean aptas para participar, independientemente del motivo, incluidas afecciones médicas o clínicas, o participantes potencialmente en riesgo de no cumplir los procedimientos del estudio.
6. Hipersensibilidad conocida a algunos de los principios activos o excipientes del RT o ICG (incluido historial previo de hipersensibilidad a productos que contengan albúmina humana).
7. Hipersensibilidad al ioduro de sodio.
8. Pacientes alérgicos al yodo.
9. Pacientes con hipertiroidismo clínico, adenomas tiroideos autónomos y alteraciones autónomas focales y difusas de glándula tiroides.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with intraoperative detection of GCs.

Proporción de pacientes con detección intraoperatoria de GCs.

E.5.1.1

Timepoint(s) of evaluation of this end point

day 14

día 14

E.5.2

Secondary end point(s)

1. Number of sentinel lymph nodes (GC) biopsied during surgery after injection of the hybrid [99mTc] Tc-albumin nanocoloid-ICG (hybrid RT) or radiotracer [99mTc] Tc-albumin nanocoloid (RT) by myometrial injection guided by transvaginal ultrasound (TUMIR).
2. Number of sentinel lymph nodes with lymph node infiltration detected during surgery after injection of the hybrid RT or RT by transvaginal ultrasound-guided myometrial injection (TUMIR).
3. Number of lymph nodes with lymph node infiltration detected in the lymphadenectomy piece after injection of the hybrid RT or RT by transvaginal ultrasound-guided myometrial injection (TUMIR).
4. Number of false negative results after injection of hybrid RT or RT by transvaginal ultrasound-guided myometrial injection (TUMIR). False negatives will be defined as the number of patients with lymph node infiltration in at least one lymph node of the lymphadenectomy piece and sentinel node negative for lymph node infiltration.
5. Difference in the number of GC visualized after injection of the hybrid RT or RT between TUMIR lymphogammagraphy and cervical lymphogammagraphy.
6. Difference in the drainage pattern of each radiotracer (hybrid RT and RT) between cervical injection and transvaginal ultrasound-guided myometrial injection (TUMIR).

7. Causes of non-drainage of hybrid RT or RT in cervical injection or in transvaginal ultrasound-guided myometrial injection (TUMIR).
8. Difference between the proportion of paraortic GC detected after injection of each of the radiotracers (hybrid RT and RT) during surgery.
9. Proportion of patients with hypersensitivity reactions related to the injection of each of the two radiotracers (hybrid RT and RT).
10. Proportion of patients with adverse events related to the injection of one of the two radiotracers (hybrid RT and RT).
11. Surgical detection time of GCs during intraoperative detection after injection of each of the two radiotracers (hybrid RT and RT).
12. Histological data of the tumor: histology, tumor grade, tumor size and myometrial infiltration

1. Número de ganglios centinela (GC) biopsiados durante la cirugía tras la inyección del radiotrazador híbrido [99mTc]Tc-nanocoloide de albúmina-ICG (RT híbrido) o de radiotrazador [99mTc]Tc-nanocoloide de albúmina (RT) mediante inyección miometrial guiada por ecografía transvaginal (TUMIR).
2. Número de ganglios centinela con infiltración ganglionar detectados durante la cirugía tras la inyección del RT híbrido o del RT mediante inyección miometrial guiada por ecografía transvaginal (TUMIR).
3. Número de ganglios linfáticos con infiltración ganglionar detectados en la pieza de linfadenectomía tras la inyección del RT híbrido o del RT mediante inyección miometrial guiada por ecografía transvaginal (TUMIR).
4. Número de resultados falsos negativos tras la inyección del RT híbrido o del RT mediante inyección miometrial guiada por ecografía transvaginal (TUMIR). Los falsos negativos se definirán como número de pacientes con infiltración ganglionar en al menos un ganglio linfático de la pieza de linfadenectomía y ganglio centinela negativo para infiltración ganglionar.
5. Diferencia en el número de GC visualizados tras la inyección del RT híbrido o del RT entre la linfogammagrafía TUMIR y la linfogammagrafía cervical.
6. Diferencia en el patrón de drenaje de cada radiotrazador (RT híbrido y RT) entre la inyección cervical y la inyección miometrial guiada por ecografía transvaginal (TUMIR).

7. Causas de no drenaje del RT híbrido o del RT en la inyección cervical o en la inyección miometrial guiada por ecografía transvaginal (TUMIR).
8. Diferencia entre la proporción de GC paraórticos detectados tras la inyección de cada uno de los radiotrazadores (RT híbrido y RT) durante la cirugía.
9. Proporción de pacientes con reacciones de hipersensibilidad relacionadas con la inyección de cada uno de los dos radiotrazadores (RT híbrido y RT).
10. Proporción de pacientes con acontecimientos adversos relacionados con la inyección de alguno de los dos radiotrazadores (RT híbrido y RT) .
11. Tiempo de detección quirúrgica de los GCs durante la detección intraoperatoria tras la inyección de cada uno de los dos radiotrazadores (RT híbrido y RT).
12. Datos histológicos del tumor: histología, grado tumoral, tamaño tumoral e infiltración miometrial.

E.5.2.1

Timepoint(s) of evaluation of this end point

28 days

28 días

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

LVLS

Última visita 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

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

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)

No aplica

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

2020-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-12-20

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