Clinical Trials Register

Summary
EudraCT Number:	2014-001764-35
Sponsor's Protocol Code Number:	M14-361
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:	2014-09-22
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

2014-001764-35

A.3

Full title of the trial

A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination with Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer.

Estudio fase 1 de escalada de dosis y fase 2, aleatorizado y doble ciego, de veliparib en combinación con carboplatino y etopósido como terapia en pacientes naive en cáncer de pulmón microcítico en estadio amplio

A.3.1

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

A Phase 1 dose-finding and Phase 2 randomized double-blinded study evaluating if veliparib compared to placebo improves efficacy of caboplatin and etoposide combination in patients with untreated extensive stage small cell lung cancer

Estudio en Fase 1 y Fase 2 aleatorizado y doble ciego para evaluar si veliparib mejora la eficacia de la combinación de carboplatino y etopósido en comparación con un placebo en pacientes con cáncer de pulmón no tratado previamente.

A.4.1

Sponsor's protocol code number

M14-361

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+34901 20 01 03
B.5.6	E-mail	abbvie_reec@abbvie.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	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	Veliparib 20 mg
D.3.2	Product code	ABT-888
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Veliparib
D.3.9.1	CAS number	912444-00-9
D.3.9.2	Current sponsor code	ABT-888
D.3.9.3	Other descriptive name	VELIPARIB
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	20
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	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	Veliparib 40 mg
D.3.2	Product code	ABT-888
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Veliparib
D.3.9.1	CAS number	912444-00-9
D.3.9.2	Current sponsor code	ABT-888
D.3.9.3	Other descriptive name	VELIPARIB
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	40
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: 3
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	Veliparib 100 mg
D.3.2	Product code	ABT-888
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Veliparib
D.3.9.1	CAS number	912444-00-9
D.3.9.2	Current sponsor code	ABT-888
D.3.9.3	Other descriptive name	VELIPARIB
D.3.9.4	EV Substance Code	SUB32392
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	100
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Extensive Stage Disease Small Cell Lung Cancer (ED SCLC)

Cáncer de pulmón microcítico en estadio avanzado

E.1.1.1

Medical condition in easily understood language

Advanced Small Cell Lung Cancer

Cáncer de pulmón de células pequeñas en estadio avanzado

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10041068
E.1.2	Term	Small cell lung cancer extensive stage
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

The Phase 1 primary objective is to establish the maximum tolerated dose and the recommended Phase 2 dose for veliparib in combination with carboplatin and etoposide in subjects with untreated extensive stage disease small cell lung cancer and to evaluate the pharmacokinetic interaction between veliparib and etoposide.
The Phase 2 primary objective is to evaluate if veliparib vs. placebo in combination with carboplatin and etoposide followed by veliparib vs. placebo as maintenance monotherapy results in improved progression free survival (PFS).

El objetivo principal de la fase 1 es Determinar la dosis máxima tolerada (DMT) y la dosis recomendada para la fase 2 (DRF2) de veliparib en combinación con carboplatino y etopósido en pacientes con cáncer de pulmón microcítico en estadio avanzado no tratados previamente y evaluar la interacción farmacocinética entre veliparib y etopósido.

El objetivo principal de la fase 2 es Evaluar si veliparib en combinación con carboplatino y etopósido, seguido de veliparib en monoterapia de mantenimiento, mejora la supervivencia sin progresión (SSP) en comparación con placebo en combinación con carboplatino y etopósido, seguido de placebo en monoterapia, en pacientes con CPM en estadio avanzado no tratados previamente.

E.2.2

Secondary objectives of the trial

The secondary objectives of Phase 1 are to evaluate the safety of
maintenance veliparib monotherapy in subjects completing 4 cycles of
combination therapy.
The secondary objectives of Phase 2 are to assess the effects of veliparib combination therapy followed by veliparib maintenance monotherapy on overall survival (OS), to assess the effects of veliparib combination therapy at the time of its completion on the objective response rate (ORR), to assess the effect of veliparib combination therapy followed by placebo maintenance on PFS and OS, and to further evaluate the safety of veliparib in combination with carboplatin and etoposide followed by veliparib maintenance monotherapy.

mantenimiento en una dosis de 400 mg dos veces al día en los pacientes que completen 4 ciclos de la terapia de combinación

Los objetivos secundarios de la fase 2 evaluar los efectos de la terapia de combinación con veliparibveliparib seguido de monoterapia de mantenimiento de veliparib en la supervivencia global, evaluarlos efectos de la terapia de combinación de veliparib mejora la tasa de respuestas objetivas (TRO) en el momento de finalización del tratamiento combinado, evaluar el efecto de la terapia de combinación de veliparib seguida de mantenimiento con placebo en la supervivencia global y supervicencia sin progresión y evaluar más detenidamente la seguridad de veliparib en combinación con carboplatino y etopósido, seguido de veliparib en monoterapia de mantenimiento.

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

Pharmacogenetic substudy: optional blood test;
Pharmacodynamic substudies - blood tests and tissue if available

Subestudio farmacogenético: Análisis de sangre opcional
Subestudio farmacodinamia. Análisis de sangre y tejido si está disponible.

E.3

Principal inclusion criteria

-Phase 2 subjects must have histologically or cytologically confirmed ED SCLC with measurable disease.
-ECOG performance score 0 or 1.
-Phase 1 subjects may have other pre-defined small cell tumors but measurable disease is not required.
-Subjects must have adequate hematologic, renal and hepatic function.

El paciente para la fase 2 debe presentar un CPM en estadio avanzado confirmado mediante histología o citología que ha sido diagnosticado recientemente y no ha recibido quimioterapia previa.
El paciente presenta una puntuación funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1.
Los pacientes para la fase 1 pueden tener otros tumores de células pequeñas previamente definidos pero no se requiere enfermedad medible
El paciente debe tener una función hematológica, renal y hepática adecuada

E.4

Principal exclusion criteria

-Subject has had any prior chemotherapy, radiotherapy, investigations anti-cancer agents or biologic therapy for SCLC.
-Subject has known hypersensitivity to etoposide or platinum agents.
-Subject currently has or has a history of central nervous system (CNS) or leptomeningeal metastasis.
-Subject has a history or seizures within 12 months of first dose of study drug.
Subject has history of hepatitis B or C within 3 months of screening.

El paciente ha recibido cualquier quimioterapia, radioterapia, antineoplásico experimental o tratamiento biológico para el cáncer de pulmón microcítico
El paciente presenta hipersensibilidad a etopósido, compuestos de platino
El paciente presenta metástasis activas en el sistema nervioso central (SNC) o leptomeníngeas o antecedentes de metástasis en el SNC o leptomeníngeas
El paciente tiene antecedentes de convulsiones en los 12 meses anteriores a la primera dosis de medicación del estudio.
El paciente presenta antecedentes de hepatitis B o C en los tres meses anteriores a la selección.

E.5 End points

E.5.1

Primary end point(s)

Phase 1: Dose Limiting Toxicity
Phase 2: Progression Free Survival

Fase 1. Dosis tóxica limitante
Fase 2. Supervivencia sin progresión

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 1: Safety assessments through the end of cycle one of each dose level.
Phase 2: radiographic every 6 weeks the first 24 weeks, then every 9 weeks; clinical progression evaluated at all study visitis.

Fase 1. Evaluaciones de seguridad de cada nivel de dosis hasta el final del ciclo 1
Fase 2. Progresión clínica evaluada en todas las vistas del estudio mediante radiografías cada 6 semanas en las primeras 24 semanas, después cada 9 semanas

E.5.2

Secondary end point(s)

Adverse events during Phase 1 and Phase 2;
Objective response rates, duration of response, and overall survival for Phase 2.

Acontecimientos adversos durante la fase 1 y la fase 2.
Tasas de respuesta objetiva, duración de la respuesta y supervivencia global para la fase 2.

E.5.2.1

Timepoint(s) of evaluation of this end point

Adverse events: from the first dose of study drugs to 30 days from final visit;
OS: up to 2 years from the first dose of study drugs;
DOR and ORR: from the first on-study radiographic assessment to radiographic or clinical disease progression;

Acontecimientos adversos desde la primera dosis de la medicación del estudio hasta 30 días después de la visita final
Supervivencia global; Hasta 2 años después de la primera dosis de la medicación del estudio.
Duración de la respuesta global (DRG) y tasa de respuesta objetiva (TRO) desde la primera evaluación radiográfica del estudio o progresión clínica de la enfermedad.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Performance Status (ECOG)

Puntuación Funcional (ECOG)

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose escalation and pharmacokinetics study

Estudio de escalado de dosis y de farmacocinética

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

Australia

Belarus

Canada

Korea, Democratic People's Republic of

Netherlands

New Zealand

Puerto Rico

Russian Federation

Spain

Taiwan

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 defined as the date of last subject's last visit. The sponsor may also end the study upon confirmation that the primary endpoint was statistically met.

El final del estudio se define como la fecha de la última visita del último paciente. El promotor puede finalizar el estudio después de la confirmación del que se ha alcanzado estadísticamente el objetivo primario.

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

E.8.9.2

In all countries concerned by the trial 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:

100

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

F.4.2.2

In the whole clinical trial

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)

Upon completion of the study, the subjects will be treated in accordance with the Investigator's best clinical judgement.

Tras la finalización del estudio, los sujetos serán tratados de acuerdo al criterio del investigador

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

2014-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-27

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