Clinical Trials Register

Summary
EudraCT Number:	2013-004321-83
Sponsor's Protocol Code Number:	GEFCAPI04
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:	2013-12-05
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

2013-004321-83

A.3

Full title of the trial

A randomised phase III trial comparing a strategy based on molecular analysis to the empiric strategy in patients with carcinoma of an unknoun primary (CUP)

Ensayo Clínico Aleatorizaco de Fase III comparando una estrategia basada en el análisis molecular con la estrategia empírica en pacientes con carcinoma de origen primario desconocido (CUP)

A.3.1

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

CUP Trial

Ensayo CUP

A.4.1

Sponsor's protocol code number

GEFCAPI04

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 Català d'Oncologia (ICO)
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	Institu Català d'Oncologia (ICO)
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	MFAR S.L.
B.5.2	Functional name of contact point	Federico Nepote
B.5.3	Address:
B.5.3.1	Street Address	c/ Secretari Coloma, 64-68, escalera B, entlo. 5ª
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08024
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034934 34 44 12
B.5.5	Fax number	0034932 53 11 68
B.5.6	E-mail	investigacion@mfar.net

D. IMP Identification
D.IMP: 1
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	Cisplatino Ferrer Farma 1mg/ml, concentrado para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferrer Farma, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Suspension for injection
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	CISPLATIN
D.3.9.2	Current sponsor code	PR1
D.3.9.4	EV Substance Code	SUB07483MIG
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	1
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	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	Gemcitabina STADA polvo para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratorio STADA, S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Powder for solution for injection/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	GEMCITABINE
D.3.9.1	CAS number	95058-81-4
D.3.9.2	Current sponsor code	PR2
D.3.9.4	EV Substance Code	SUB07892MIG
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	1000
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

Carcinomas of an unknown primary site (CUP)

Carcinomas de origen primario desconocido

E.1.1.1

Medical condition in easily understood language

Cancer which first localization remains unknown

Cáncer en donde la localización primaria es desconocida

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Compare empiric chemotherapy regimen in patient with CUP (cisplatin-gemcitabine) with standard treatment of the primary suspected by molecular analysis, by means of PFS

Comparar régimen empírico de la quimioterapia con la estrategia basada por el análisis molecular en pacientes con carcinoma de origen primario desconocido (cisplatino-gemcitabina) mediante la SLP

E.2.2

Secondary objectives of the trial

Response Rate, tolerance, overall survival, pharmacogenomics, translational study.

Tasa de respuestas, tolerancia, supervivencia global, farmacogenómica y estudios traslacionales

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

Blood-sample sub-study, version 3.0, date 21 /06 /2013
Objectives: Identify genetic factors involved in the response to treatment with gemcitabine and cisplatin.

Tumor-sample sub-study, version 3.0, date 21 /06 /2013
Objectives: Validate an academic test which determine the most likely tumor site.

Estudio de muestras sanguíneas, versión 3.0 del 21/06/2013
Objetivos: Identificar los factores genéticos implicados en la respuesta al tratamiento con gemcitabina y cisplatino.

Estudios de muestras de tumor, versión 3.0 del 21/06/2013
Objetivos: Validar un estudio académico que determine la localización primaria mas probable.

E.3

Principal inclusion criteria

1) Patients presenting with carcinoma of an unknown primary, confirmed by histo-pathological analysis (including an immunohistochemical analysis) and corresponding to one of the following histologic types: moderately or well-differentiated adenocarcinoma, poorly-differentiated adenocarcinoma, undifferentiated carcinoma, squamous-cell carcinoma.
2) Diagnostic work-up in keeping with Standard Options Recommandations des CAPI (Lesimple et al., 2003).
3) Age>18 years.
4) Performance status 0, 1 or 2 according to ECOG.
5) Good or poor prognosis CUP classified according to the GEFCAPI classification.
6) CUP with at least one measurable lesion.
7) Tumour sample available for molecular analysis.
8) CUP not belonging to a subgroup requiring a specific treatment.
9) Satisfactory haematological, renal and hepatic function.
10) Cardiac, respiratory and neurological function compatible with the administration of cisplatin chemotherapy.
11) No previous chemotherapy, for CUP.
12) Previous radiotherapy is acceptable, but it should be completed at least 4 weeks before the start of systemic treatment. Randomisation can be performed during this time frame.
13) All patients with reproductive potential must practice an effective method of birth control throughout the study. Female patients with childbearing potential must have a negative pregnancy test within 7 days before study treatment.
14) Information delivered to patient and informed consent form signed by the patient or legal representative.

1 ) Los pacientes que presentan carcinoma de localización primaria desconocida, confirmados por análisis histopatológico (incluyendo un análisis inmunohistoquímico) y que corresponda a uno de los siguientes tipos histológicos: adenocarcinoma moderadamente o bien diferenciado, adenocarcinoma pobremente diferenciado, carcinoma indiferenciado, carcinoma de células escamosas.
2 ) Diagnóstico en consonancia con las recomendaciones estándar de CAPI (Lesimple et al. , 2003).
3 ) Edad> 18 años .
4 ) Estado funcional 0, 1 o 2 de acuerdo con ECOG .
5 ) CUP de buen o mal pronóstico de acuerdo a la clasificación GEFCAPI .
6 ) CUP con al menos una lesión medible.
7 ) Muestra disponible para el análisis molecular del tumor .
8 ) CUP que no pertenecen a un subgrupo que requiere un tratamiento específico.
9 ) Adecuada función hematológica, renal y hepática .
10 ) Función cardiaca, respiratoria y neurológica compatible con la administración de quimioterapia con cisplatino.
11 ) Ausencia de quimioterapia previa para CUP.
12 ) Se acepta radioterapia previa, pero debe haberse completado al menos 4 semanas antes del inicio del tratamiento sistémico. La aleatorización se puede realizar durante este intervalo de tiempo.
13 ) Todos los pacientes con potencial reproductivo deben practicar un método efectivo de control de la natalidad durante todo el estudio. Mujeres en edad fértil deben disponer de una prueba de embarazo negativa, en los 7 días previos al inicio del tratamiento a estudio.
14) Firma del Consentimiento Informado por el paciente o su representante legal

E.4

Principal exclusion criteria

1) Patients in whom the diagnosis has not been histologically confirmed (a cytological analysis alone does not permit patient entry onto the trial).
2) Patients with known HIV infection.
3) Patients with symptomatic brain metastases.
4) Associated disease likely to prevent the patient from receiving the treatment.
5) Previous history of cancer (excepted skin basocellular epithelioma or epithelioma in situ of the uterine cervix) during the 5 years before study entry.
6) Patients already included in another clinical trial with an experimental therapy.
7) Pregnant women, and women who are breastfeeding.
8) Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons.

1) Pacientes en los que el diagnóstico no se ha confirmado histológicamente (un análisis citológico solo, no permite la entrada de pacientes en el ensayo).
2) Pacientes con infección por VIH conocida.
3) Pacientes con metástasis cerebrales sintomáticas.
4) Enfermedad concurrente que impidan que el paciente reciba el tratamiento.
5) Historia previa de cáncer en los 5 años anteriores al ingreso al estudio (excepto: epitelioma basocelular de piel o epitelioma in situ del cuello uterino)
6) Pacientes ya incluidos en otro ensayo clínico con terapia experimental.
7) Las mujeres embarazadas y/o en período de lactancia.
8) Imposibilidad de cumplir con el seguimiento médico del ensayo debido a a razones geográficas, sociales o psicológicas.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival according to RECIST criteria v1.1.

Supervivencia libre de progresión según criterios RECIST v1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

5.5 years

5.5 años

E.5.2

Secondary end point(s)

1. Response rate (RECIST criteria) v1.1.
2. Tolerance (NCI-CTC criteria version 4.0).
3. Overall survival.
4. Pharmacogenomics: Genetic polymorphisms in genes involved in cisplatin and gemcitabine metabolism (blood lymphocytes).
5. Translational studies.
6. Medico-economic study (Medical costs and utilities).

1. Tasa de respuestas (según RECIST V 1.1)
2. Tolerancia (NCI-CTC versión 4.0)
3. Supervivencia Global
4. Farmacogenómica: Polimorfismos genéticos implicados en el metabolismo de cisplatino y gemcitabina (linfocitos)
5. Estudios traslacionales
6. Estudios medico-económicos (recursos médicos utilizados)

E.5.2.1

Timepoint(s) of evaluation of this end point

5.5 years

5.5 años

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

Yes

E.6.4

Safety

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

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

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

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

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

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:

223

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

223

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

193

F.4.2.2

In the whole clinical trial

233

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)

Clinical normal practise

Práctica clínica habitual

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

2014-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-13

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

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