Clinical Trials Register

Summary
EudraCT Number:	2010-018476-24
Sponsor's Protocol Code Number:	MO22162
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-07-28
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

Denmark - DHMA

A.2

EudraCT number

2010-018476-24

A.3

Full title of the trial

A prospective double-blind randomized Phase III study of 300 mg vs. 150 mg erlotinib in current smokers with locally advanced or metastatic NSCLC in second-line setting after failure on chemotherapy

A.3.1

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

A study of 300 mg vs. 150 mg erlotinib in current smokers with locally advanced or metastatic NSCLC in second-line setting after failure on chemotherapy

A.3.2

Name or abbreviated title of the trial where available

CURRENTS

A.4.1

Sponsor's protocol code number

MO22162

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Roche Registration Limited
B.5.2	Functional name of contact point	Head, EU/ROW
B.5.3	Address:
B.5.3.1	Street Address	6 Falcon Way, Shire Park
B.5.3.2	Town/ city	Welwyn Garden City, Hertfordshire
B.5.3.3	Post code	AL7 1TW
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44(0)1707366000
B.5.5	Fax number	+44(0)1707384127
B.5.6	E-mail	welwyn.eudract@roche.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	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.3.4	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.3.9.2	Current sponsor code	RO 50-8231
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.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	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.3.4	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.3.9.2	Current sponsor code	RO 50-8231
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	Film-coated tablet
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	Film-coated tablet
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

Locally advanced (stage IIIB with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), or metastatic (stage IV) non-small cell lung cancer (NSCLC)

E.1.1.1

Medical condition in easily understood language

Locally advanced or metastatic non-small cell lung cancer (NSCLC)

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
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

To compare the efficacy of two dose levels of erlotinib (150 mg and 300 mg) on progression-free survival (PFS) in current smokers with stage IIIB/IV NSCLC after failure of first-line platinum-based chemotherapy.

E.2.2

Secondary objectives of the trial

1. To compare the efficacy of the 150 mg vs. 300 mg erlotinib dose with respect to response and disease control rates, and overall survival.

To assess the safety of the 300 mg erlotinib dose as a second-line therapy.

To compare the plasma concentrations from both doses of erlotinib.

To assess the effects of both doses of erlotinib on QOL.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Disease Specific Inclusion Criteria:
1. Histologically or cytologically documented inoperable, locally advanced (stage IIIB with supraclavicular lymph node metastases or malignant pleural or pericardial effusion) or metastatic (stage IV) NSCLC disease.
2. Measurable disease must be characterized according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Eisenhauer et al., 2009).
3. Must have received one prior platinum-based chemotherapy regimen for advanced NSCLC and now exhibit PD, and must have recovered from any treatment-related toxicity.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Life expectancy ≥ 12 weeks.
6. Current cigarette smoker (having smoked > 100 cigarettes in entire lifetime and currently smoking on average ≥ 1 cigarette per day), not intending to stop smoking during the study.
7. Adequate hematological function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, and
• Platelet count ≥ 100 x 109/L, and
• Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level).
8. Adequate liver function:
• Total bilirubin < 1.5 x upper limit of normal (ULN), and
• AST, ALT < 2.5 x ULN in patients without liver metastases; < 5 x ULN in patients with liver metastases.
9. Adequate renal function:
• Serum creatinine ≤ 1.25 x ULN,
• Creatinine clearance ≥ 60 ml/min.
10.Female patients must be either: a) postmenopausal (24 months of amenorrhea), b) surgically sterile or c) not pregnant (negative urine or serum pregnancy test within 3 days of randomization).
Male patients must be surgically sterile or agree to use a barrier method of contraception.
Female and male patients must be willing to use an effective method of contraception during the trial and for 60 days after last administration of erlotinib. Acceptable methods of contraception include an established hormonal therapy or intrauterine device for females, or the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicide.
General Inclusion Criteria:
11.Patients able and willing to give written informed consent. The consent must be obtained before the first screening procedure.
12.Males or females aged ≥ 18 years.
13.Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
14.Patients able to read, and understand the local language(s) for which the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaires are available.

E.4

Principal exclusion criteria

Cancer Treatment Related Exclusion Criteria:
1. Received prior therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor).
2. Received radiotherapy within 28 days prior to enrolment.
3. Received treatment with any other investigational agent, or participated in another clinical trial, with the following exceptions:
• Chemotherapy-only trials are permitted including where chemotherapy in combination with bevacizumab has been used (if study drug completed ≥ 28 days prior to receiving the first dose of Erlotinib).
• Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before receiving the first dose of study drug.
• Prior surgery is permitted if performed ≥ 4 weeks before receiving the first dose of study drug and the patient is fully recovered.
• Prior localized radiotherapy is permitted if it was not administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented, and provided it has been completed ≥ 4 weeks before receiving the first dose of study drug.
• Participation in a methodological or observational study in which no investigational agent was given.
4. Received more than one line of chemotherapy (first-line maintenance chemotherapy after first-line platinum-based chemotherapy is allowed) for locally advanced/metastatic NSCLC.
Cancer Related Exclusion Criteria:
5. History of breast cancer or melanoma at any time, or history of another malignancy in the last 5 years with the exception of the following:
• Other malignancies cured by surgery alone and having a continuous disease-free
interval of ≥ 5 years.
• Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix.
6. History or symptomatic evidence of brain metastases.
Other Study Drug Related Exclusion Criteria
7. Known hypersensitivity to erlotinib or any of its excipients.
8. Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. The use of contact lenses is not recommended during the study. The decision to continue to wear contact lenses should be discussed with the patient’s treating oncologist and the
ophthalmologist.
9. Coumarins (CoumadinTM; warfarin) use. If the patient requires anti-coagulation therapy, then the use of low molecular weight heparin instead of coumarins is recommended where clinically possible.
General Exclusion Criteria
10.Unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
11.Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
12.Female patients of childbearing potential who are: a) pregnant according to urine or serum pregnancy test within 3 days of randomization, b) breast-feeding. Female and male patients of reproductive potential not willing to use an effective method of
contraception during the trial and for 60 days after last administration of erlotinib.
13.Patients with pre-existing parenchymal lung disease such as pulmonary fibrosis, lymphangiosis carcinomatosis.
14.Patients with known infection with HIV, HBV, HCV. Testing is not required in the absence of clinical signs and symptoms suggestive of these conditions.
15.Patients assessed by the investigator to be unable or unwilling to comply with the
requirements of the protocol.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival, defined as the length of time between randomization and the date of the first occurrence of disease progression or death.

E.5.1.1

Timepoint(s) of evaluation of this end point

Clinical and safety assessments will be performed at Screening and Baseline and on Day 1 of every 6th week until PD, death, or unacceptable toxicity.

E.5.2

Secondary end point(s)

● To compare the efficacy of the 150 mg vs. 300 mg erlotinib doses with respect to response and disease control rates, and overall survival.
● To assess the safety of the 300 mg erlotinib doses as a secondline therapy.
● To compare the plasma concentrations from both doses of erlotinib.
● To assess the effects of both doses af erlotinib on quality of life (QOL)

E.5.2.1

Timepoint(s) of evaluation of this end point

Clinical and safety assessments will be performed at Screening and Baseline and on Day 1 of every 6th week until PD, death, or unacceptable toxicity.

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

the comparator is a higher dose of erlotinib (300 mg vs. 150 mg)

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

Denmark

France

Germany

Lithuania

Netherlands

Portugal

Spain

Sweden

Switzerland

Turkey

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

The study will end when the last patient has stopped erlotinib therapy and completed their last visit.

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.1.3

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

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

170

F.4.2.2

In the whole clinical trial

300

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)

At the end of the study (upon database lock), patients still receiving treatment will be unblinded. Any patients who are receiving the experimental dose of erlotinib at the end of the study will continue to be provided with erlotinib on an ongoing basis through clinical trial supply, until disease progression, death, unacceptable toxicity or patient/clinician decsion to stop this therapy

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

2010-08-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-08-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-07

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