Clinical Trials Register

Summary
EudraCT Number:	2016-004353-32
Sponsor's Protocol Code Number:	GECP16/06
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:	2017-07-21
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-004353-32

A.3

Full title of the trial

Survival, quality of life and self-reported outcomes of elderly patients with advanced non-small cell lung cancer (NSCLC), treated with pembrolizumab (MK-3475) in the first line setting

Ensayo clínico Fase II para evaluar la supervivencia, la calidad de vida y los resultados percibidos por el paciente en pacientes ancianos con cáncer de pulmón no microcítico tratados en primera línea con Pembrolizumab

A.3.1

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

Pembrolizumab (MK-3475) in elderly patients with non-small cell lung cancer

Estudio con el fármaco Pembrolizumab en pacientes ancianos con cancer de pulmón

A.3.2

Name or abbreviated title of the trial where available

PEBEL

A.4.1

Sponsor's protocol code number

GECP16/06

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	Spanish Lung Cancer Group (SLCG/GECP)
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	Spanish Lung Cancer Group (SLCG/GECP)
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	Spanish Lung Cancer Group (SLCG/GECP)
B.5.2	Functional name of contact point	Eva Pereira
B.5.3	Address:
B.5.3.1	Street Address	Avenida Meridiana, 358, 6a planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08027
B.5.3.4	Country	Spain
B.5.4	Telephone number	34934302006205
B.5.5	Fax number	34934191768
B.5.6	E-mail	epereira@gecp.org

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.2.1.1.2	Name of the Marketing Authorisation holder	Merk Sharp and Dhome
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.3.1	Product name	Pembrolizumab
D.3.2	Product code	MK-3475
D.3.4	Pharmaceutical form	Powder for 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	PEMBROLIZUMAB
D.3.9.1	CAS number	1374853-91-4
D.3.9.2	Current sponsor code	MK-3475
D.3.9.3	Other descriptive name	Anti-PD-1 monoclonal body
D.3.9.4	EV Substance Code	SUB167136
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	25
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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

First line treatment in PD-L1 positive advanced non-small cell lung cancer patients

Primera línea de tratamiento en pacientes PD-L1 positivo con cáncer de pulmón no microcítico.

E.1.1.1

Medical condition in easily understood language

First line treatment in advanced lung cancer patients

Pacientes con cáncer de pulmón avanzado en primera línea de tratamiento.

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

To determine the efficacy, in terms of overall survival at one year, of first-line treatment with Pembrolizumab (MK-3475) in elderly patients with advanced NSCLC expressing PD-L1.

Determinar la eficacia, en términos de supervivencia global en un año, del tratamiento de primera línea con Pembrolizumab (MK-3475) en pacientes ancianos con NSCLC avanzado que expresan PD-L1.

E.2.2

Secondary objectives of the trial

To evaluate changes in health-related quality of life in responder and non-responder patients according to the QLQ-C30, the LCSS and the QLQ-ELD14 questionnaires.
To evaluate the impact on functional, cognitive and nutritional geriatric assessments of subjects.
To describe the Objective Response Rate (ORR), and the Progression-free Survival (PFS), according to RECIST criteria.
To assess the median disease-specific survival (DSS) and the Overall Survival rate at 2 years.
To describe the safety and tolerability profile of first-line pembrolizumab (MK-3475) in previously untreated elderly patients with advanced NSCLC expressing PD-L1.

Evaluar los cambios en la calidad de vida en pacientes respondedores y no respondedores según los cuestionarios QLQ-C30, LCSS y QLQ-ELD14.
Evaluar el impacto en las evaluaciones geriátricas funcionales, cognitivas y nutricionales de los sujetos.
Describir la Tasa de Respuesta Objetiva (RO) y la Supervivencia libre de progresión (SLP), de acuerdo con los criterios RECIST.
Definir la Tasa de supervivencia media para una enfermedad específica y la Tasa de Supervivencia general en dos años.
Describir el perfil de seguridad y tolerabilidad del pembrolizumab (MK-3475) en primera línea de tratamiento en pacientes ancianos no tratados previamente con NSCLC avanzado y que expresan PD-L1.

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

Description of PD-L-1 expression in previously untreated elderly patients with advanced NSCLC

Descripción de la expresión de PD-L-1 en pacientes ancianos no tratados previamente y con NSCLC avanzado.

E.3

Principal inclusion criteria

- Patients with histologically or cytological documented stage IIIB or IV squamous and non-squamous non-small-cell lung cancer previously untreated.
- EGFR and ALK have to be wild-type.
- The subject must be willing and able to provide written informed consent/assent for the trial.
- Patients must be aged >70 years, on day of signing informed consent.
- PD-L1 expression ≥ 1%
- ECOG 0 - 1
- Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

- Pacientes con cáncer de pulmón no microcítico de células escamosas o no escamosas, histológica o citológicamente documentado, en estadio IIIB o IV sin tratamiento previo.
- EGFR y ALK 'wild type'.
- El sujeto debe estar dispuesto y ser capaz de proporcionar el consentimiento informado.
- Los pacientes deben tener >70 años de edad el día de la firma del consentimiento informado.
- Enfermedad medible (al menos 1 lesión) basada en los criterios RECIST v1.1. Los pacientes no serán elegibles si esta lesión fue irradiada antes de la inclusión.
- Expresión de PD-L1 ≥ 1%
- ECOG 0 - 1
- Los sujetos masculinos en edad fértil deben acordar el uso de un método anticonceptivo adecuado, comenzando con la primera dosis de la terapia del estudio hasta 120 días después de la última dosis de terapia del estudio.

E.4

Principal exclusion criteria

- Is currently participating and receiving study therapy or has participated in a study within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose over 10 mg of prednisone or equivalent, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Hypersensitivity to Pembrolizumab or any of its excipients.
- Has a known history of active TB (Bacillus Tuberculosis)
- Has had any prior anti-cancer therapy for his or her metastatic NSCLC. In the case of patients who have progressed to a metastatic stage after having been treated for early stage NSCLC, chemotherapy or radiation therapy as part of this previous treatment is allowed, provided they have been completed more than three months ago. Patients who received adjuvant or neoadjuvant treatment or both for early stages will be eligible for this trial.
- Has had any previous malignancy (except non melanoma skin cancer, and cancer in situ of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast), unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate if they are stable and have no evidence of new or enlarging brain metastases, and are not using steroids at a dose over 10 mg of prednisone or equivalent, for at least 7 days prior to trial treatment
- Patient has active autoimmune disease that has required systemic treatment in the past 2 years
- Has any geriatric exclusion criteria: advanced dementia (GDS ranking >6), - moderate or severe functional dependence (Barthel Index < 35) or Life expectancy less than one year, due to co-morbidities other than lung cancer.
- Evidence of interstitial lung disease.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has a known history of Human Immunodeficiency Virus, active Hepatitis B or Hepatitis C.
- Has an active infection requiring systemic therapy

- Pacientes que actualmente esten participando y recibiendo terapia de estudio o hayan participado en un estudio en las 4 semanas anteriores a la primera dosis de tratamiento.
- Tiene un diagnóstico de inmunodeficiencia o está recibiendo tratamiento sistémico con esteroides a una dosis superior a 10 mg de prednisona o equivalente, o cualquier otra forma de terapia inmunosupresora en los 7 días previos a la primera dosis del tratamiento de prueba.
- Hipersensiblidad al Pembrolizumab o alguno de sus excipientes.
- TB activo (Bacillus Tuberculosis)
- Pacientes con terapia anti-cancerígena para CPNM metastásico. En el caso de pacientes que hayan progresado a un estadio metastásico después de ser tratados para un estadio temprano de CPNM, está permitido que estén tratados con quimioterapia o radioterapia como tratamiento previo, siempre que se haya completado hace más de tres meses. Pacientes que reciben tratamiento adyuvante o neoadyuvante para estadios tempranos también serán elegibles para el estudio.
- El paciente haya tenido malignidad previa (exceptuando cáncer de piel no melanomatoso, o cáncer in situ de: vejiga, gástrico, colon, cervical / displasia, melanoma, mama) a menos que se logre una remisión completa 2 años antes de la entrada en el estudio y que no requieran terapia adicional durante el periodo del estudio.
- Pacientes con metástasis en sistema nervioso central (SNC) y/o meningitis carcinomatosa. Los sujetos con metástasis cerebrales previamente tratadas pueden participar si son estables y no tienen evidencia de metástasis cerebrales nuevas o de agrandamiento, y no están usando esteroides en una dosis de más de 10 mg de prednisona o equivalente, durante al menos 7 días antes del tratamiento en estudio.
- Paciente con enfermedad autoinmune activa que ha requerido tratamiento sistémico en los últimos 2 años.
- Tiene algún criterio de exclusión geriátrica: demencia avanzada (clasificación GDS> 6), dependencia funcional moderada o grave (índice de Barthel <35) o esperanza de vida inferior a un año, debido a comorbilidades distintas del cáncer de pulmón.
- Evidencia de enfermedad pulmonar intersticial.
- Historial de trastornos psiquiátricos o abuso de sustancias que podrían interferir con la cooperación en los requisitos del estudio.
- Historial de Virus de la immunodeficiència humana, Hepatitis B o Hepatitis C activas.
- Tiene una infección activa que requiere terapia sistémica.

E.5 End points

E.5.1

Primary end point(s)

To determine the efficacy, in terms of overall survival at one year, of first-line treatment with Pembrolizumab (MK-3475) in elderly patients with advanced NSCLC expressing PD-L1.

Determinar la eficacia, en términos de supervivencia global en un año, del tratamiento de primera línea con Pembrolizumab (MK-3475) en pacientes ancianos con NSCLC avanzado que expresan PD-L1.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year recruiting patients
2 years of treatment with Pembrolizumab (MK-3475)
At least 1 year of follow up

1 año de reclutamiento
2 años de tratamiento con Pembrolizumab (MK-3475)
Al menos un año de seguimiento.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year recruiting patients
2 years of treatment with Pembrolizumab (MK-3475)
At least 1 year of follow up

1 año de reclutamiento
2 años de tratamiento con Pembrolizumab (MK-3475)
Al menos un año de seguimiento.

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Treatment with MK-3475 will continue until two years of therapy have been administered, documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator’s decision to withdraw the subject, subject withdraws consent, noncompliance with trial treatment or procedure requirements, or administrative reasons. MK-3475 treated subjects who attain a complete response may consider stopping trial treatment.

El tratamiento con MK-3475 durará 2 años, también puede finalizarse el estudio en el caso de progresión de la enfermedad, efectos adversos inaceptables, enfermedad intercurrente que impida la administración del tratamiento, la decisión del investigador de retirar el sujeto, el sujeto retira el consentimiento, el incumplimiento del ensayo o razones administrativas. También se realizará la visita de final de tratamiento en aquellos sujetos que obtengan una respuesta completa al tratamiento.

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)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

None

Ninguno

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

2017-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-27

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

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