Clinical Trials Register

Summary
EudraCT Number:	2008-006323-31
Sponsor's Protocol Code Number:	D1532C00016
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-31
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2008-006323-31

A.3

Full title of the trial

A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 (Hyd-Sulfate) in Combination with Docetaxel, Compared with Docetaxel Alone, in 2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB – IV)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

D1532C00016

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASTRAZENECA
B.1.3.4	Country	Italy
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	AZD6244
D.3.2	Product code	AZD6244
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	606143-52-6
D.3.9.2	Current sponsor code	AZD6244
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	75
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	TAXOTERE
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Docetaxel
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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, hard
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

2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB–IV)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	PT
E.1.2	Classification code	10029521

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10029522

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	PT
E.1.2	Classification code	10059515

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 assess the efficacy in terms of PFS of AZD6244 in combination with docetaxel, compared with docetaxel alone, in 2nd line patients with KRAS mutation positive locally advanced or metastatic NSCLC

E.2.2

Secondary objectives of the trial

1.To further assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in 2nd line patients with KRAS mutation positive locally advanced or metastatic NSCLC 2.To assess the safety and tolerability profile of AZD6244 in combination with docetaxel 3.To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (CFDNA) for the analysis of KRAS mutation status. 4.To investigate the pharmacokinetics (PK) of AZD6244 and N-desmethyl AZD6244 and any other known metabolites when AZD6244 is administered in combination with docetaxel.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of signed, written and dated informed consent prior to any study specific procedures 2. Male or female, aged 18 years or older 3. Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV) 4.Failure of 1st line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) in advanced disease or subsequent relapse of disease following 1st line therapy. See Appendix L for further details. See Section 5.2 for specific 1st line agents not permitted in this study. 5. WHO Performance Status 0 – 1 6. Patients must be eligible to receive treatment with docetaxel in accordance with docetaxel product information (available from Sanofi-Aventis, the manufacturer of docetaxel – see Appendix J for contact details) 7. At least one lesion, not previously irradiated, that can be accurately measured as &#8805;10 mm in the longest diameter (LD) with spiral computed tomography (CT) scan or as &#8805;20 mm with conventional techniques (conventional CT, MRI) and which is suitable for accurate repeated measurements 8. Tumour sample confirmed as KRAS mutation positive (Note: Sample must be available upon enrolment to ship to AZ appointed central laboratory, or mutation status confirmed locally at AstraZeneca agreed local laboratory using a) allele specific PCR (this includes ARMS™) or b) direct sequencing) 9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Post menopausal females are defined as follows: natural menopause with menses >1 year ago; or radiation-induced oophorectomy with last menses >1 year ago; or chemotherapy-induced menopause with 1 year interval since last menses; or serum FSH and LH and plasma oestradiol levels in the postmenopausal range for the institution; or bilateral oopherectomy or hysterectomy. 10. Serum creatinine clearance >50mL/min by either Cockcroft-Gault formula or 24hr urine collection analysis 11. Patients should be able to swallow AZD6244/placebo capsules.

E.4

Principal exclusion criteria

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous randomisation of treatment in the present study 3. Mixed small cell and non-small cell lung cancer histology 4. Received >1 prior anti-cancer therapy for advanced or metastatic NSCLC (excluding radiotherapy, see exclusions 6 and 9) 5. Having received an investigational drug within the 30 days prior to entry, or have not recovered from side effects of an investigational drug 6. Receiving or have received systemic anti-cancer therapy within 4 weeks prior to starting study treatment (6 weeks for nitrosoureas, mitomycin, and suramin) 7. Prior treatment with a MEK inhibitor or any docetaxel containing regimen (prior treatment with paclitaxel is acceptable) 8. Any unresolved toxicity >CTCAE Grade 2 from previous anti-cancer therapy, apart from alopecia 9. The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 2 weeks of the first dose of study treatment 10. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment.

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS)

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

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

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.8.3

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

Information not present in EudraCT

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

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

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	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	Yes
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	10
F.4.2	For a multinational trial
F.4.2.1	In the EEA	36
F.4.2.2	In the whole clinical trial	80

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

2009-03-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-02-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-09-22

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