Clinical Trials Register

Summary
EudraCT Number:	2012-000644-94
Sponsor's Protocol Code Number:	VA_2012/01
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-09-03
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

France - ANSM

A.2

EudraCT number

2012-000644-94

A.3

Full title of the trial

A randomized phase II trial assessing Sorafenib (Nexavar®) in combination with irinotecan in metastatic colorectal cancer patients with KRAS mutated tumours after failure of all active drugs known to be effective.

A.3.2

Name or abbreviated title of the trial where available

NEXIRI 2

A.4.1

Sponsor's protocol code number

VA_2012/01

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	Centre Val d’Aurelle - Paul Lamarque
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Centre Val d’Aurelle - Paul Lamarque
B.5.2	Functional name of contact point	Dr Jean-Pierre BLEUSE
B.5.3	Address:
B.5.3.1	Street Address	208, rue des apothicaires
B.5.3.2	Town/ city	Montpellier cedex 5
B.5.3.3	Post code	34298
B.5.3.4	Country	France
B.5.4	Telephone number	04 67 61 31 02
B.5.5	Fax number	04 67 61 30 23
B.5.6	E-mail	jean-pierre.bleuse@montpellier.unicancer.fr

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.2.1.1.1	Trade name	NEXAVAR
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER SANTE
D.2.1.2	Country which granted the Marketing Authorisation	France
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	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	SORAFENIB
D.3.9.1	CAS number	284461-73-0
D.3.9.3	Other descriptive name	protein kinase inhibitor
D.3.9.4	EV Substance Code	SUB23139
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	200
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

metastatic colorectal cancer

E.1.1.1

Medical condition in easily understood language

advanced colorectal cancer

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10052362
E.1.2	Term	Metastatic colorectal 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

To evaluate the median progression free survival defined as the time from randomization to disease progression according to RECIST criteria (Version 1.1) or death from any cause

E.2.2

Secondary objectives of the trial

- Disease control rate and response rate
- Treatment-related toxicity (NCI CTC V4.0)
- Overall survival
- Quality of life

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

- Pharmacokinetic
- Pharmacogenetic
- Predictive CTC biomarkers studie
- Predictive tumoral biomarkers studie
- CTC studie

E.3

Principal inclusion criteria

- Male or female ≥ 18 years old
- Histologically confirmed diagnosis of colorectal cancer
- Asymptomatic or resected primary tumor
- Metastatic colorectal cancer not eligible for curative surgery
- At least one target lesion:
- Unidimensionally measurable on cross-sectional imaging
- In an area not previously irradiated
- Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan, oxaliplatin, bevacizumab)
- WHO performance status ≤ 2
- Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases
- Total bilirubin ≤ 1.5 ULN, ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
- Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3
- Amylase and lipase < 1.5 ULN
- Serum creatinine ≤ 1.5 ULN
- Negative pregnancy test in women of childbearing potential
- Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment
- Life expectancy > 3 months
- Informed consent signed prior any study specific procedures.

E.4

Principal exclusion criteria

- History of Gilbert’s syndrome
- Symptomatic brain metastases or carcinomatous meningitis
- Bone-only metastases
- History or presence of other cancer within the past 5 years (except curatively treated nonmelanoma skin cancer)
- Prior surgery or radiotherapy within 4 weeks before entering the study
- Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin), unstable cardiac disease, myocardial infarction within the previous 6 months, > grade II NYHA heart failure, uncontrolled hypertension
- History of epileptic seizures requiring long-term anticonvulsant therapy
- History of organ transplantation with use of immunosuppression therapy
- Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.3.0)
- HIV infection
- Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and ketoconazole
- Pregnant or breastfeeding women
- Bowel malabsorption or extended bowel resection that could affect the absorption of sorafenib, occlusive syndrom, inability to take oral medications
- Inflammatory bowel disease with chronic diarrhea (NCI N+Bethesda ≥ 1.2g)
- Participation in another clinical trial 30 days prior to study entry
- Concurrent treatment with any other investigational product or anticancer therapy (except for irinotecan or sorafenib)
- Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up).

E.5 End points

E.5.1

Primary end point(s)

The primary assessment criterion is the median progression free survival (PFS), evaluated according to the RECIST criteria (v1.1) by chest-abdomen-pelvis CT-scan every 8 weeks. A complete or partial response will have to be confirmed 4 weeks after the initial observation. All responses will be reviewed by a panel of independent radiologists.

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	159

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

2012-06-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-12

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

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