Clinical Trials Register

Summary
EudraCT Number:	2013-001494-24
Sponsor's Protocol Code Number:	EC-120888
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:	2013-09-16
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

2013-001494-24

A.3

Full title of the trial

A Randomized Prospective Trial of Adjuvant Chemotherapy in Patients with Completely Resected Stage I Non-Squamous Non-Small Cell Lung Cancer Identified as High Risk by the Pervenio? Lung RS Assay

Ensayo prospectivo aleatorizado de quimioterapia adyuvante en pacientes con cáncer de pulmón de célula no pequeña, no epidermoide, estadío I y resección completa, identificados de alto riesgo según el test Pervenio?

A.3.1

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

Clinical trial with or without chemotherapy after surgical resection of the primary lung cancer in patients with high risk of relapse based on the Pervenio? Lung RS Assay

Ensayo clínico con o sin quimioterapia después de la resección quirúrgica de un tumor primario de pulmón en pacientes con alto riego de recaída basado en el test Pervenio?

A.4.1

Sponsor's protocol code number

EC-120888

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	Encore Clinical, 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	Life Technologies Corporation
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	Hannover Clinical Trial Center GmbH
B.5.2	Functional name of contact point	Prof. Dr. Heiko E. von der Leyen
B.5.3	Address:
B.5.3.1	Street Address	Carl-Neuberg-Str. 1
B.5.3.2	Town/ city	Hannover
B.5.3.3	Post code	30625
B.5.3.4	Country	Germany
B.5.4	Telephone number	00495115333330
B.5.5	Fax number	004951153333399
B.5.6	E-mail	vdleyen@clinical-trial-center.de

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.2.1.1.1	Trade name	CISPLATIN
D.2.1.1.2	Name of the Marketing Authorisation holder	FERRER FARMA
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	CISPLATIN
D.3.9.1	CAS number	64.569
D.3.9.2	Current sponsor code	SUB07483MIG
D.3.9.3	Other descriptive name	Cisplatin Ferrer Farma
D.3.9.4	EV Substance Code	SUB07483MIG
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.2.1.1.1	Trade name	VINORELBINE
D.2.1.1.2	Name of the Marketing Authorisation holder	PIERRE FABRE
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	VINORELBINE
D.3.9.1	CAS number	71486-22-1
D.3.9.4	EV Substance Code	SUB00069MIG
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

Completely resected stage I non-squamous non-small cell lung cancer (NSCLC)

Pacientes resecados completamente, estadío I, con cáncer de pulmón no microcítico (CPNM)

E.1.1.1

Medical condition in easily understood language

Lung Cancer

Cáncer de pulmón

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025044
E.1.2	Term	Lung cancer
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

The primary objective of this study is to compare OS in patients with resected, stage I nonsquamous NSCLC who are found to be at high risk by the Pervenio? Lung RS Assay and who are subsequently randomized to either observation or adjuvant therapy with four cycles of cisplatin plus vinorelbine, so as to document the benefit of personalizing patient care based on
molecular prognostic data.

E.2.2

Secondary objectives of the trial

1. To compare DFS in patients randomized to each study arm.
2. To further document the previously documented of survival curves among high- and low-risk patients identified by the Pervenio? assay in this prospective cohort of stage I non- squamous NSCLC patients.
3. To collect fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissue specimens from a subset of patients with consent for full clinical annotation for future analysis of molecular and genetic correlates of disease.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent (the informed consent document must have been approved by the appropriate Institutional Review Board/Independent Ethics Committee (IRB/IEC). Consent
must be obtained and signed and witnessed PRIOR to any study specific activity.
2. Age ? 18 years
3. Able to comply with the protocol, including follow-up especially for anticipated length of study (i.e. 5 years from the initiation of enrollment).
4. Histologically documented completely resected (R0) Stage I non-squamous NSCLC. Eligible resections include lobectomy, bi-lobectomy, sleeve lobectomy and pneumonectomy.
Resections via segmentectomy or wedge resection will not be eligible. Complete resection must also be accompanied, at a minimum, by intra-operative systematic mediastinal lymph
node sampling. Systematic sampling is defined as removal of at least one representative lymph node each from levels 4 and 7 for a right-sided cancer and from levels 5 and/or 6 and 7 for left-sided cancers. Complete mediastinal lymph node dissection (MLND), however, is preferred, and is defined as resection of all lymph nodes at those same levels for right- and
left-sided cancers.
5. Adequate tissue sample available for Pervenio testing (paraffin block with tumor occupying at least 25% of the tissue surface area)
6. Life expectancy excluding NSCLC diagnosis ? 5 years
7. ECOG performance status 0-1
8. Adequate haematological function*:
a. Absolute neutrophil count (ANC) ? 1500 cells/mm3 AND
b. Platelet count ? 100000 cells/mm3 AND
c. Haemoglobin ? 9 g/dL (may be transfused to maintain or exceed this level)
9. Adequate liver function*:
a. Total bilirubin < 1.5 x upper limit of normal (ULN) AND
b. Aspartate amiotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
10. Adequate renal function*, with Serum creatinine ? 1.5 x ULN
11. Completely healed incisions
*Note: all laboratory values must be obtained within 14 days prior to randomization

E.4

Principal exclusion criteria

1. Final pathologic diagnosis on resected specimen is squamous cell histology
2. Evidence of greater than stage I pathologic staging, including loco-regional regional (hilar) or mediastinal lymph node involvement or nodal enlargement that has not been biopsied, or
of distant metastatic disease (lesions that have been biopsy-proven or that are suspicious on brain MRI and/or PET scan)
3. Evidence of incomplete resection, including positive resection margins, additional suspect nodules
4. Pregnant or lactating women
5. Women with an intact uterus (unless amenorrhoeic for the previous 24 months) unwilling to use an effective means of contraception (including oral contraceptive, intrauterine
contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last
administration of study chemotherapy. Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of study chemotherapy.
6. Active infection, either systemic or at site of primary resection
7. Any pre-operative systemic chemotherapy or treatment with an anti-cancer agent
8. Any pre-or post operative radiotherapy to primary site or elsewhere
9. Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate
cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent
10. Treatment with any investigational drug or participation in another clinical trail within 28 days prior to enrollment.
11. Known hypersensitivity to any of the study treatment agents.
12. Evidence of any other disease including infection (see above) such as neurologic or metabolic dysfunction or physical examination finding giving reasonable suspicion of a
disease or condition that contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment related complications.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is the duration of overall survival (OS) in patients determined to be at High-Risk by the Pervenio? Lung RS assay.

E.5.1.1

Timepoint(s) of evaluation of this end point

OS is defined to be the time from randomization to death.
Patients alive at the end of the analysis will be censored at their last known alive date.

E.5.2

Secondary end point(s)

1. Key Secondary Endpoint: Disease-free survival (DFS)
2. An additional secondary endpoint of the trial is to compare overall survival (OS) in patients identified by the Pervenio RS assay as high-risk stage I non-squamous NSCLC randomized to observation (Arm A) with patients identified by the Pervenio RS assay as low-risk stage I non-squamous NSCLC.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Time from randomization to disease recurrence, new primary lung cancer, or death from any cause. Patients without events at the end of the analysis will be censored at their last known event-free date.
2. OS is defined to be the time from randomization to death. Patients alive at the end of the analysis will be censored at their last known alive date.

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

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 (without chemotheray)

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

China

France

Germany

Spain

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

LVLS

Última visita del último paciente

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:

700

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

350

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

250

F.4.2.2

In the whole clinical trial

1050

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

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

2013-10-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-14

P. End of Trial
P.	End of Trial Status	Completed

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