Clinical Trials Register

Summary
EudraCT Number:	2010-023081-52
Sponsor's Protocol Code Number:	ENGOT-EN2-DGCG
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:	2013-06-10
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

2010-023081-52

A.3

Full title of the trial

A phase III Trial of postoperative chemotherapy or no further treatment for patients with node-negative stage I-II intermediate or high risk endometrial cancer.

Ensayo fase III de quimioterapia posoperatoria frente a ningún tratamiento posterior en pacientes con cáncer de endometrio de riesgo intermedio o alto, en estadios I o II, con ganglios negativos

A.3.1

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

A phase III clinical trial for patients with node-negative stage I-II intermediate or high risk endometrial cancer where the patients will be divided into 2 groups; chemotherapy after surgery versus observation only.

Un ensayo clínico de fase III para pacientes con cáncer endometrial en estadios I y II intermedia o cáncer endometrial de alto riesgo donde los pacientes se dividieron en 2 grupos, la quimioterapia después de la cirugía versus observación solamente.

A.3.2

Name or abbreviated title of the trial where available

ENGOT-EN2-DGCG EORTC 55102

A.4.1

Sponsor's protocol code number

ENGOT-EN2-DGCG

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	Danish Gynaecological Cancer Group
B.1.3.4	Country	Denmark
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	Danish Gynaecological Cancer Group
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	European Organisation for the Research and Treatment of Cancer
B.5.2	Functional name of contact point	Regulatory Affairs Department
B.5.3	Address:
B.5.3.1	Street Address	Avenue E. Mounier, 83/11
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1200
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32 (0) 2 774 1023
B.5.5	Fax number	+32 (0) 2 774 1030
B.5.6	E-mail	regulatory@eortc.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	Yes
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	Concentrate for 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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.4	EV Substance Code	SUB09583MIG
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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	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.2.1.2	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 infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CARBOPLATIN
D.3.9.1	CAS number	41575-94-4
D.3.9.4	EV Substance Code	SUB06614MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

Node-negative stage I-II intermediate or high risk endometrial cancer

cáncer endometrial en estadios I y II, de mediano y alto riesgo

E.1.1.1

Medical condition in easily understood language

Endometrial cancer

Cáncer endometrial

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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10014738
E.1.2	Term	Endometrial cancer stage I
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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10014739
E.1.2	Term	Endometrial cancer stage II
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 compare overall survival (OS) of patients treated with adjuvant chemotherapy or to observation.

Patients with medium and high-risk stage I and II endometrial cancers have, despite radical surgery, a rather high risk for progression.

Combination chemotherapy regimen of paclitaxel-carboplatin is proposed in this study, as this combination is effective and well tolerated.

comparar la supervivencia global (SG) de los pacientes tratados con quimioterapia adyuvante oa observación la eficacia de la quimioterapia de combinación adyuvante en un ensayo de fase III de asignación aleatoria, en comparación con ningún tratamiento posterior en pacientes de estadios I y II, de mediano y alto riesgo, con ganglios negativos.

E.2.2

Secondary objectives of the trial

?Disease Specific Survival (DSS)
?Progression-Free Survival (PFS)
?Toxicity (both acute and late)
?Compliance
?Quality of Life (QOL) and symptom control will be assessed using EORTC QLQ-C30 and EORTC-QLQ-EN34
?Rate of isolated pelvic relapse
?Rate of isolated distant relapse
?Rate of mix local and distant relapse

Supervivencia global ? SG (criterio de valoración primario)

Supervivencia específica de la enfermedad ? SEE
Supervivencia libre de enfermedad ? SLP
Toxicidad
Cumplimiento
Calidad de vida
Índice de recidiva pélvica aislada (central o de pared pélvica)
Índice de recidiva distante aislada
Índice de recidiva mixto, local y distante

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Full details in the protocol section 14; TRANSLATIONAL RESEARCH substudies; pages 45-49

Todos los detalles en la sección 14 del Protocolo; subestudios investigación traslacional, páginas 45-49

E.3

Principal inclusion criteria

Target Population
1.Only node-negative patients are eligible: Histological confirmed endometrial carcinoma with no macroscopic remaining tumour after primary surgery and lymph-node negative disease, with one of the following postoperative FIGO 2009 stage and grade:
a.Stage I grade 3 endometrioid adenocarcinoma
b.Stage II endometrioid adenocarcinoma
c.Stage I and II type 2 histology (clear cell, serous, or squamous cell carci-noma, or undifferentiated carcinoma)
2. Patients with prior therapy:
a. Patients have undergone hysterectomy (total abdominal hysterectomy (TAH), radical hysterectomy, laparoscopic or robotic hysterectomy) and & bilateral salpingo-oopherectomy (BSO) (or RH) and+ pelvic lymphadenectomy (LNE) within the past 10 weeks.
b. LNE: minimum 12 pelvic nodes (6 from each side) should be removed. Para-aortic LNE is optional
c. Omentectomy strongly recommended in type 2 disease (clear cell, serous, squamous cell carcinoma or undifferentiated carcinoma)
d. Surgery performed within 10 weeks of randomization. If the dates for hys-terectomy and lymph node dissection are different, 10 weeks are counted from the last surgery, and in that case the gap between two surgeries should not exceed 8 weeks.
3. Other inclusion criteria
a. Patients must give informed consent according to the rules and regulations of the individual participating centres
b. Patients have not received any other anticancer therapy other than surgery.
c. Adjuvant vaginal brachytherapy is not recommended, though permitted in both arms. In chemotherapy arm, VBT timing of VBT should not cause delay in chemotherapy delivery.
d. Patients must have WHO performance status of 0-2
e. Patients must have an adequate bone-marrow, renal and hepatic function (WBC ?3.0x109/L, neutrophils ?1.5x109/L, platelets ?100x109/L, total S-bilirubin <2 x upper normal value, ALAT <2.5 x upper normal value, estimated GFR >50 ml/min (measured or calculated according to Cockroft-Gault or Jeliffe). Up to 5% deviation for hematological values and 10% deviation for s-bilirubin and ALAT are tolerated.
f. Life expectancy of at least 12 weeks
g. Patients must be fit to receive combination chemotherapy
h. Patient?s age >18 years

Población diana
1. Solo son elegibles las pacientes con ganglios negativos: carcinoma endometrial con confirmación histológica, sin restos de tumor macroscópico tras la cirugía primaria, sin enfermedad en los ganglios linfáticos y con uno de los siguientes estadios y grados FIGO 2009 postoperatorios:
a. adenocarcinoma endometrioide en estadio I, grado 3;
b. adenocarcinoma en estadio II;
c. Estadios I y II, histología tipo 2 (carcinoma de células claras, serosas, de células escamosas o carcinoma no diferenciado).
Terapia anterior
2. Las pacientes han sido sometidas a una histerectomía (histerectomía abdominal total, histerectomía radical, histerectomía laparoscópica o robótica) y a una salpingo-ooforectomía bilateral (BSO) y linfadenectomía pélvica (LNE).
3. LNE: deben extirparse al menos 12 ganglios pélvicos (6 de cada lado). La LNE paraaórtica es opcional.
4. Se recomienda encarecidamente una omentectomía en carcinoma de células claras, serosas, escamosas o carcinoma no diferenciado
5. Cirugía realizada dentro de las 10 semanas anteriores a la asignación aleatoria. Si las fechas de la histerectomía y de la disección de ganglios linfáticos son diferentes, se cuentan 10 semanas desde la última cirugía, y en ese caso el lapso entre ambas cirugías no debe ser de más de 8 semanas.
6. Las pacientes deben dar un consentimiento informado conforme a las normas y reglamentaciones de cada centro participante.
7. Las pacientes no deben haber recibido otras terapias contra el cáncer salvo la cirugía.
8. La braquiterapia vaginal adyuvante está permitida en ambas ramas. En la rama de quimioterapia, la BTV no debe retrasar el calendario de quimioterapia.
9. Las pacientes deben tener un estado funcional de la OMS de entre 0 y 2.
10. Las pacientes deben tener una función medular, renal y hepática adecuada (recuento de glóbulos blancos ?3,0x109/l, neutrófilos ?1,5x109/l, plaquetas ?100x109/l, bilirrubina total en suero <2 veces el valor normal superior, ALT <2,5 es el valor normal superior, IFG estimado >50 ml/min. (medido o calculado según Cockroft-Gault o Jeliffe). Se toleran hasta un 5% de desviación de valores hematológicos y un 10% de desviación para bilirrubina en suero y ALT.
11. Esperanza de vida de al menos 12 meses.
12. Las pacientes deben estar preparadas para recibir quimioterapia de combinación.
13. Las pacientes deben tener >18 años de edad.

E.4

Principal exclusion criteria

1. Target disease exclusions:
?Carcinosarcoma, Sarcomas or small cell carcinoma with neuroendocrine differen-tiation.
2. Prohibited Treatments and/or Therapies
?External Beam Radiotherapy
?Concurrent cancer therapy
?Concurrent treatment with an anticancer investigational agent or participation in another anticancer clinical trial
3. Other exclusion criteria
?Previous or concurrent malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin
?Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed
?Whatever reasons which interferes with an adequate follow-up

Excepciones de enfermedad diana
1. Carcinosarcoma, sarcomas o carcinoma de células pequeñas con diferenciación neuroendocrina.
Tratamientos y/o terapias prohibidas
2. Radioterapia de haz externo.
3. Terapia oncológica simultánea.
4. Tratamiento simultáneo con un agente anticanceroso experimental o participación en otro ensayo clínico anticanceroso.
Otros criterios de exclusión
5. Enfermedad maligna anterior o simultánea, salvo casos de carcinoma in situ de cuello de útero o carcinoma de células basales de la piel tratados con intención curativa.
6. Infección activa u otra afección médica grave subyacente que pudiera impedir que la paciente recibiera tratamiento o someterse a seguimiento.
7. Cualquier razón que interfiera con un seguimiento adecuado.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this trial is overall survival.

supervivencia global (SG)

E.5.1.1

Timepoint(s) of evaluation of this end point

Survival is calculated from the date of randomization until the date of death.

La supervivencia se calculó a partir de la fecha de la aleatorización hasta la fecha de la muerte.

E.5.2

Secondary end point(s)

? Disease Specific Survival (DSS)
? Progression-Free Survival (PFS)
? Toxicity (both acute and late)
? Compliance
? Quality of Life (QOL)
? Rate of isolated pelvic relapse (central or pelvic wall)
? Rate of isolated distant relapse
? Rate of mix local and distant relapse

E.5.2.1

Timepoint(s) of evaluation of this end point

Survival is calculated from the date of randomization until the date of death.
The DSS is calculated from the date of randomization until the date of death caused by cancer, Patients who die of non-disease-related causes are censored at time of death.
The PFS is calculated as time elapsed from date of randomization to date of progression or death of disease, whichever is the first registered event. Vaginal, pelvic and distant relapses will be registered.
QoL will be registered during whole study period.
Toxicity will be graded according to the Common Terminology for Adverse Events (CTCAE v4.0)

La supervivencia se calculó a partir de la fecha de la aleatorización hasta la fecha de la muerte.
El DSS se calcula a partir de la fecha de la aleatorización hasta la fecha de la muerte causada por el cáncer, los pacientes que mueren de causas no relacionadas con la enfermedad son censurados en el momento de la muerte.
El PFS se calcula como el tiempo transcurrido desde la fecha de la aleatorización hasta la fecha de la progresión de la enfermedad o la muerte, el que sea el primer evento registrado. Se registrarán recaídas vaginales, pélvica y distante.
La calidad de vida se registró durante el período de estudio conjunto.
Toxicidad será calificado de acuerdo con la terminología común para Eventos Adversos (CTCAE v4.0)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Observation

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

Belgium

Denmark

France

Germany

Italy

Netherlands

Poland

Portugal

Spain

Switzerland

United Kingdom

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

It is expected to include 678 patients in 3-4 years period and have overall survival available by another 3-4 years

Se espera incluir 678 pacientes en período de 3-4 años y tienen una supervivencia global a disposición por otros 3-4 años

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