Clinical Trials Register

Summary
EudraCT Number:	2014-000370-19
Sponsor's Protocol Code Number:	CO-1686-022
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:	2015-07-31
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2014-000370-19

A.3

Full title of the trial

TIGER-1: A Randomized, Open-label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients with EGFR-Mutant Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC)

TIGER-1: Estudio de Fase II/III, aleatorizado, abierto, de CO-1686 o erlotinib como primera línea de tratamiento de pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)

A.3.1

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

A Phase 2/3 clinical study to evaluate the safety and efficacy of the study medication CO-1686 compared to erlotinib in subjects with Non-Small Cell Lung Cancer

Ensayo clínico de fase II/III para evaluar la seguridad y la eficacia de la medicación en estudio CO-1686 comparado con erlotinib en pacientes con cáncer de pulmón no microcítico

A.3.2

Name or abbreviated title of the trial where available

TIGER-1

A.4.1

Sponsor's protocol code number

CO-1686-022

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	Clovis Oncology, Inc.
B.1.3.4	Country	United States
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	Clovis Oncology, 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	Clovis Oncology UK Ltd
B.5.2	Functional name of contact point	Dr Lindsey Rolfe
B.5.3	Address:
B.5.3.1	Street Address	Sheraton House, Castle Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB3 0AX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	900 811 335
B.5.6	E-mail	info@clovisoncology.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	CO-1686
D.3.2	Product code	CO-1686
D.3.4	Pharmaceutical form	Film-coated tablet
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	Not applicable
D.3.9.1	CAS number	1446700-26-0
D.3.9.2	Current sponsor code	CO-1686
D.3.9.3	Other descriptive name	CO-1686
D.3.9.4	EV Substance Code	SUB126980
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	125
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	CO-1686
D.3.2	Product code	CO-1686
D.3.4	Pharmaceutical form	Film-coated tablet
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	Not applicable
D.3.9.1	CAS number	1446700-26-0
D.3.9.2	Current sponsor code	CO-1686
D.3.9.3	Other descriptive name	CO-1686
D.3.9.4	EV Substance Code	SUB126980
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	250
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	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	Tarceva
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	Erlotinib
D.3.2	Product code	Erlotinib
D.3.4	Pharmaceutical form	Film-coated tablet
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	ERLOTINIB
D.3.9.1	CAS number	183321-74-6
D.3.9.3	Other descriptive name	ERLOTINIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB16423MIG
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	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: 4
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	Tarceva
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	Erlotinib
D.3.2	Product code	Erlotinib
D.3.4	Pharmaceutical form	Film-coated tablet
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	ERLOTINIB
D.3.9.1	CAS number	183321-74-6
D.3.9.3	Other descriptive name	ERLOTINIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB16423MIG
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.IMP: 5
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	Tarceva
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	Erlotinib
D.3.2	Product code	Erlotinib
D.3.4	Pharmaceutical form	Film-coated tablet
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	ERLOTINIB
D.3.9.1	CAS number	183321-74-6
D.3.9.3	Other descriptive name	ERLOTINIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB16423MIG
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	150
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

First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)

Tratamiento de primera línea en pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)

E.1.1.1

Medical condition in easily understood language

First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)

Tratamiento de primera línea en pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10029514
E.1.2	Term	Non-small cell lung cancer NOS
E.1.2	System Organ Class	100000004864

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 the antitumor efficacy of oral single-agent CO-1686 with that of erlotinib as measured by PFS, when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced/metastatic NSCLC

Comparar la eficacia antitumoral del monotratamiento con CO-1686 por vía oral, con respecto a la del erlotinib, en función del SSP, administrado como tratamiento específico de primera línea en pacientes con CPNMC avanzado/metastásico y EGFR mutado

E.2.2

Secondary objectives of the trial

- To compare secondary measures of clinical efficacy ORR, DR,and OS following treatment with CO-1686 versus erlotinib
- To assess PFS, ORR, DR, and OS in patients with baseline T790M mutations based on central allele-specific polymerase chain reaction (PCR) EGFR mutation assay
- To assess quality of life (QOL) using the patient-reported outcomes (PRO) of European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ-LC13), the Dermatology Life Quality Index (DLQI), and the EQ-5D instrument in patients receiving CO-1686 versus erlotinib
? To evaluate safety and tolerability of CO-1686 versus erlotinib in patients with advanced/metastatic NSCLC whose tumors have EGFR-activating mutations
? To determine PK of CO-1686 in this patient population using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings

-Comparar las medidas secundarias de la eficacia clínica TRO, DR, y ST del CO-1686 en monoterapia por vía oral con las del erlotinib
-Evaluar la SSP, TRO, DR, y ST en pacientes con mutaciones T790M en el momento inicial, en función del ensayo de la mutación EGFR mediante la reacción en cadena de la polimerasa alelo-específica central
-Evaluar la calidad de vida mediante el cuestionario de RSP principal sobre calidad de vida de la Asociación Europea para la investigación y tratamiento del cáncer (EORTC QLQ-C30), el EORTC QLQ-LC13, el Índice de calidad de vida en dermatología (DLQI), y el cuestionario EQ-5D, en pacientes tratados con CO-1686, comparado con erlotinib
-Evaluar la seguridad y tolerabilidad del CO-1686 comparado con erlotinib en pacientes con CPNMC con tumores con mutaciones activadoras del EGFR
-Determinar la FC del CO-1686 en estos pacientes empleando métodos de FC poblacional (FCPOB) y buscar correlaciones entre FC, exposición, respuesta y/o datos de seguridad

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

To explore tissue and blood-based biomarkers that may be predictive of response or primary resistance to CO-1686 or erlotinib and investigate mechanisms of acquired resistance to treatment with CO-1686 or erlotinib using patient tumor tissue and blood samples

Buscar biomarcadores tisulares y sanguíneos que pudieran predecir una respuesta o bien una resistencia primaria al CO-1686 o erlotinib, e investigar mecanismos de resistencia adquirida al tratamiento con CO-1686 o erlotinib en muestras de tejido tumoral y muestras de sangre de los pacientes

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent NSCLC
2. Documented evidence of a tumor with one or more activating EGFR mutations excluding exon 20 insertion
3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of planned randomization and have tissue available to send to sponsor lab or are able to undergo a biopsy during Screening and provide tissue to sponsor lab
4. Measureable disease according to RECIST Version 1.1
5. Life expectancy of at least 3 months
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
7. Age >= 18 years (in certain territories, the minimum age requirement may be higher; e.g., age >= 20 years in Japan and Taiwan)
8. Adequate hematological and biological function, confirmed by the following laboratory values e.g. Bone Marrow Function, Hepatic Function, Renal function and Electrolyte within normal range

1. CPNMC avanzado a nivel local y no operable/metastásico, confirmado histológica o citológicamente
2. Prueba confirmada de un tumor con mutaciones que activen el EGFR, mediante análisis a nivel local excluyendo inserciones en el exón 20
3. Pacientes que se hayan sometido a una biopsia o resección quirúrgica de tejido tumoral, ya sea primario o metastásico, en los 60 días anteriores al día del tratamiento del estudio y cuenten con tejido biopsiado disponible para enviarlo a los laboratorios del promotor, o bien sean aptos para someterse a una biopsia durante la selección y proporcionar tejido a dichos laboratorios del promotor
4. Enfermedad medible según RECIST, versión 1.1
5. Esperanza de vida de al menos 3 meses
6. Escala de estado funcional del Grupo Oncológico Cooperativo del Este (de EE. UU.) (ECOG) de entre 0 y 1
7. Edad >= 18 años (en algunos países la edad mínima necesaria puede ser mayor, por ejemplo >= 20 en el caso de Japón y Taiwán)
8. Actividad sanguínea y biológica suficiente, confirmada mediante las valoraciones analíticas siguientes: Actividad de la médula ósea, Actividad hepática, Actividad renal y Electrolitos dentro de límites normales

E.4

Principal exclusion criteria

1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
-Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
4. Known pre-existing interstitial lung disease (ILD)
5. Brain metastases
6. Treatment with prohibited medications [e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment (except corticosteroids and megesterol acetate), or immunotherapy] =< 14 days prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
7. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication (not known to affect QT interval) prior to C1D1
8.Prior treatment with EGFR TKIs, CO-1686 or other drugs that target mutant EGFR
9. Cardiac abnormalities or history
10. Non-study related surgical procedures =< 7 days prior to C1D1. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
11. Females who are pregnant or breastfeeding
12. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of CO-1686 and 2 weeks after the last dose of erlotinib
13. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
14. Any other reason the investigator considers the patient should not participate in the study

1. Prueba documentada de una mutación activadora por inserción en el exón 20 del gen para EGFR
2. Tratamiento anterior con quimioterapia citotóxica para CPNMC avanzado; la quimioterapia antineoplásica prequirúrgica/posquirúrgica está permitida siempre que hayan transcurrido por lo menos 6 meses entre el final de dicha quimioterapia y el momento de la aleatorización
3. Segunda neoplasia maligna activa; es decir, se sabe que el paciente padece un cáncer posiblemente mortal para el que puede (aunque no necesariamente) estar siendo tratado en la actualidad
- Los pacientes con antecedentes de neoplasia maligna que hayan sido completamente tratados y actualmente no presenten indicios de dicha neoplasia podrán inscribirse en el ensayo siempre y cuando todo el proceso quimioterapéutico haya finalizado > 6 meses antes y/o hayan recibido cualquier transplante de médula > 2 años antes del primer día del tratamiento del estudio, C1D1
4. Neumopatía intersticial (NPI) preexistente confirmada
5. Metástasis cerebrales
6. Tratamiento con medicamentos no permitidos (por ejemplo, tratamiento antineoplásico concurrente como otra quimioterapia, radioterapia, tratamiento hormonal [excepto corticosteroides y acetato de megesterol], o inmunoterapia) =< 14 días antes del primer día del tratamiento del estudio, el C1D1
7. Pacientes que actualmente estén recibiendo tratamiento con cualquier medicamento que pueda alargar el intervalo QT, si ese tratamiento no puede ni interrumpirse ni cambiarse a un medicamento diferente (que se sepa que no afecta al intervalo QT) antes del C1D1
8. Tratamiento anterior con ITC EGFR, CO-1686 u otros fármacos cuya diana sea el EGFR mutante
9. Anomalías o antecedentes cardíacos
10. Intervenciones quirúrgicas no relacionadas con el estudio =< 7 días antes del C1D1. En todos los casos, el paciente deberá encontrarse lo suficientemente recuperado y estable antes de administrársele el tratamiento.
11. Mujeres embarazadas o que están amamantando
12. Rechazar el uso de métodos anticonceptivos suficientes en pacientes fértiles (mujeres y hombres) durante el estudio y 12 semanas después de la última dosis de CO-1686, y 2 semanas después de la última dosis de erlotinib
13. Presencia de cualquier trastorno sistémico concurrente, grave o sin estabilizar, que resulte incompatible con el estudio clínico (por ejemplo, toxicomanía, enfermedad intercurrente no estabilizada incluida diabetes no controlada, infección activa, trombosis arterial y embolia pulmonar sintomática)
14. Cualquier otro motivo por el que el investigador considere que el paciente no debe participar en el estudio

E.5 End points

E.5.1

Primary end point(s)

PFS according to RECIST Version 1.1 as determined by investigator review (invPFS)

SSP según RECIST (versión 1.1) conforme lo determine el investigador mediante su evaluación (SSPinv)

E.5.1.1

Timepoint(s) of evaluation of this end point

From start of treatment until it is clear that no further clinical benefit can be achieved.

Desde el inicio del tratamiento hasta que se confirme que este no puede aportar ningún beneficio clínico

E.5.2

Secondary end point(s)

- ORR and DR according to RECIST 1.1 as determined by investigator review, and OS
- invPFS, ORR, DR, and OS in patients with baseline T790M mutations confirmed by central EGFR mutation assay
- Change from baseline in QOL as measured using the PRO of EORTC QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following treatment with CO-1686 versus erlotinib
- Treatment-emergent AEs, laboratory abnormalities and ECG abnormalities
- Plasma PK parameters for CO-1686 based on sparse sampling

- TRO y DR según RECIST (versión 1.1) conforme lo determine el investigador mediante su evaluación y la ST
- SSPinv, TRO, DR y ST en pacientes con mutaciones T790M en el momento inicial, confirmadas por ensayo central de mutación en el EGFR
- Cambio desde el momento inicial en la CDV, valorado mediante los cuestionarios RSP de EORTC QLQ-C30, EORTC QLQ-LC13, el DLQI y el EQ-5D tras el tratamiento con CO-1686 en comparación con erlotinib
- AAs durante el tratamiento, anomalías analíticas y electrocardiográficas (ECG)
- Parámetros FC en plasma para CO-1686 a partir de muestreos puntuales

E.5.2.1

Timepoint(s) of evaluation of this end point

From start of treatment until it is clear that no further clinical benefit can be achieved.

Desde el inicio del tratamiento hasta que se confirme que este no puede aportar ningún beneficio clínico

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

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

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

E.8.1.6

Cross over

Yes

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

Yes

E.8.2.3.1

Comparator description

Erlotinib

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

France

Germany

Hong Kong

Israel

Italy

Korea, Republic of

Spain

Taiwan

United States

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

Upon discontinuation of original study treatment or crossover phase, all patients will enter the follow-up phase to monitor for survival status and subsequent NSCLC approximately every 3 months (12 +/- 1 week) until death or sponsor decision, whichever comes first.

Cuando se finalice el tratamiento original del estudio, o el de la etapa de cambio de tratamiento, todos los pacientes pasarán a una fase de seguimiento para vigilar la supervivencia y posterior tratamiento para el CPNMC aproximadamente cada 3 meses (12 +/- 1 semanas), hasta el fallecimiento del paciente o hasta que el promotor decida, lo que suceda primero.

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

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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

900

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

110

F.4.2.2

In the whole clinical trial

1200

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)

After the End of treatment the patients will return to their normal SOC medication.

Los pacientes volverán a su fármaco habitual tras el fin del tratamiento

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

2015-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-07-03

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials