Clinical Trials Register

Summary
EudraCT Number:	2011-005157-31
Sponsor's Protocol Code Number:	D7913L00138
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:	2012-03-08
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

2011-005157-31

A.3

Full title of the trial

A phase II Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as treatment re-challenge in Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non- Small Cell Lung Cancer (NSCLC) and who previously responded to gefitinib and received subsequent chemotherapy or other active anti-cancer therapy excluding EGFR-TKIs

Studio di fase II in aperto, multicentrico, a singolo braccio per indagare l'efficacia, la sicurezza e la tollerabilita' di Gefitinib 250 mg (IRESSA) come trattamento ri-sfida in pazienti che hanno tumore al polmone non a piccole cellule (NSCLC) localmente avanzato o metastatico positivo alla mutazione del Recettore del Fattore di Crescita Epidermico (EGFR) e che hanno precedentemente risposto al gefitinib e ricevuto successiva chemioterapia o altra terapia anticancro ad eccezione di inibitori tirosin chinasici di EGFR.

A.3.1

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

A Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as treatment re-challenge in Patients, who have Non-Small Cell Lung Cancer (NSCLC)

Studio per indagare l’efficacia, la sicurezza e la tollerabilita' di Gefitinib 250 mg (IRESSA™) come trattamento ri-sfida in pazienti che hanno tumore al polmone non a piccole cellule (NSCLC)

A.3.2

Name or abbreviated title of the trial where available

ICARUS

A.4.1

Sponsor's protocol code number

D7913L00138

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	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	c
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASTRAZENECA SPA
B.5.2	Functional name of contact point	ASTRAZENECA SPA
B.5.3	Address:
B.5.3.1	Street Address	PALAZZO VOLTA VIA FRANCESCO SFORZA
B.5.3.2	Town/ city	BASIGLIO
B.5.3.3	Post code	20080
B.5.3.4	Country	Italy
B.5.4	Telephone number	029801 1
B.5.5	Fax number	029801 1
B.5.6	E-mail	FLORE.LATOUR@ASTRAZENECA.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	IRESSA*30CPR RIV 250MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA 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	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	GEFITINIB
D.3.9.1	CAS number	184475-35-2
D.3.9.2	Current sponsor code	ZD1839
D.3.9.4	EV Substance Code	SUB20637
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.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

Non small cell lung cancer

Tumore polmonare non a piccole cellule

E.1.1.1

Medical condition in easily understood language

Non small cell lung cancer

Tumore polmonare non a piccole cellule

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	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
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 characterise the impact of gefitinib on the
Response Evaluation Criteria in Solid
Tumours (RECIST) based assessments;
objective response rate (ORR ; confirmed
complete response(CR) or partial response
(PR)) and disease control rate (DCR;
confirmed complete response(CR) or partial response (PR) or stable disease (SD)) in patients with EGFR M+ NSCLC

Valutare il Tasso di Controllo di Malattia (DCR; risposta completa (CR) o risposta parziale (PR) o malattia stabile (SD)) a gefitinib utilizzando i criteri di valutazione “Response Evaluation Criteria in Solid Tumours” (RECIST) versione 1.1 nei pazienti con NSCLC EGFR M+

E.2.2

Secondary objectives of the trial

- To characterise the impact of gefitinib on
progression free survival according to
RECIST, in patients with EGFR M+ NSCLC
- To characterise the impact of gefitinib on
progression free survival according to clinical criteria, in patients with EGFR M+ NSCLC
- To characterise the impact of gefitinib on Duration of therapy, in patients with EGFR M+ NSCLC
- To characterise the impact of gefitinib on overall survival in patients with EGFR M+ NSCLC, in patients with EGFR M+ NSCLC
- To characterise the safety profile of gefitinib in patients with EGFR M+ NSCLC

- Valutare il Tasso di Risposta Obiettiva (ORR; risposta complete (CR) o risposta parziale (PR)), sopravvivenza libera da progressione in accordo ai RECIST, sopravvivenza libera da progressione in accordo ai criteri clinici, durata della terapia e sopravvivenza in pazienti con EGFR M+ NSCLC
- Valutare il profilo di sicurezza di gefitinib in pazienti con EGFR M+ NSCLC

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Provision of informed consent prior to any study specific procedures
2. Histologically or cytologically confirmed NSCLC with an activating sensitising
EGFR TK mutation as it was determined before starting the first gefitinib treatment
by using a well-validated and robust methodology: adenocarcinoma, including
Bronchoalveolar Carcinoma (BAC), squamous cell carcinoma, large cell carcinoma,
adenosquamous carcinoma or undifferentiated carcinoma or not-otherwise specified
NSCLC.
3. Female or male patients aged 18 years or over with Locally advanced or metastatic
stage IIIB/IV disease, not suitable for therapy of curative intent or stage IV
(metastatic) disease, eligible for gefitinib re-challenge treatment for NSCLC who
have already received gefitinib with a documented complete (CR) or partial
response (PR) or stable disease (SD) >12 weeks as the best response to their 1st
gefitinib treatment and progressing during or after a subsequent anti-cancer therapy
(excluding EGFR-TKIs) treatment, including but not limited to doublet platinum
based chemotherapy or docetaxel monotherapy or pemetrexed monotherapy.
4. Measurable disease defined as at least one lesion, not previously irradiated, that can
be accurately measured at baseline as ≥ 10 mm in the longest diameter (except
lymph nodes which must have short axis ≥ 15 mm) with spiral CT or MRI and
which is suitable for accurate repeated measurements.
5. WHO / ECOG / Zubrod performance status 0-2.

1. Firma del Consenso Informato prima di qualsiasi procedura di studio
2. NSCLC confermato istologicamente o mitologicamente con mutazione attivante di sensibilità nel dominio tirosin chinasico del gene EGFR come determinate prima dell’inizio del primo trattamento con gefitinib usando una metodologia robusta e ben validate: adenocarcinoma, includendo il carcinoma broncoalveolare (BAC), carcinoma cellular squamoso, carcinoma a grandi cellule, carcinoma adenosquamoso o carcinoma non differenziato o NSCLC non altrimenti specificato.
3. Pazienti maschi o femmine di età maggiore o uguale a 18 anni con malattia localmente avanzata o metastatica di stadio IIIB/IV, non adatti a terapia di intento curative o malattia di stadio IV (metastatica), elegibili per il trattamento re-challenge con gefitinib per il NSCLC che hanno già ricevuto gefitinib con una documentata risposta complete (CR) o risposta parziale (PR) o malattia stabile (SD) >12 settimane come miglior risposta al loro primo trattamento con gefitinib e che hanno ricevuto una successiva terapia anti-tumorale (escludendo inibitori tirosinchinasici dell’EGFR), includendo ma non limitato alla chemioterapia basata su doppietta di platino o ionoterapia con docetaxel o ionoterapia con pemetrexed.
4. Malattia misurabile definite come almeno una lesione, non precedentemente irradiate, che può essere accuratamente misurata al baseline come ≥ 10 mm nel diametro più lungo (ad eccezione dei linfonodi che devono avere l’asse corto ≥ 15 mm) con CT spirale o MRI e che sia adatto per misure accurate e ripetute.
5. WHO / ECOG / Zubrod performance status 0-2.

E.4

Principal exclusion criteria

1. Known severe hypersensitivity to gefitinib or any of the excipients of the product
Prior EGFR TKIs except gefitinib followed by subsequent anti-cancer treatment
(including chemotherapy and excluding EGFR-TKIs). Previous adjuvant
chemotherapy is allowed. Prior surgery or radiotherapy must be completed more
than 6 months before start of study treatment. Palliative radiotherapy must be
completed at least 4 weeks before start of study treatment with no persistent
radiation toxicity.
3. Progression disease or stable disease (SD) <12 weeks as best response to the 1st line
treatment with gefitinib
4. Not progressing during or after the last anti-cancer treatment.
5. Considered to require radiotherapy to the lung at the time of study entry or in the
near future
6. Past medical history of interstitial lung disease, drug-induced interstitial disease,
radiation pneumonitis which required steroid treatment or any evidence of clinically
active interstitial lung disease
7. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline
8. Insufficient lung function as determined by either clinical examination or an arterial
oxygen tension (PaO2) of < 70 Torr
9. Known or suspected brain metastases or spinal cord compression, unless treated
with surgery and/or radiation and stable without steroid treatment for at least 4
weeks prior to the first dose of study medication
10. Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer
therapy
11. Concomitant use of known CYP 3A4 inducers such as phenytoin, carbamazepine,
rifampicin, barbiturates, or St John's Wort
12. Pregnancy or breast-feeding
13. As judged by the investigator, any evidence of severe or uncontrolled systemic
disease (eg, unstable or uncompensated respiratory, cardiac, hepatic, or renal
disease)
14. Evidence of any other significant clinical disorder or laboratory finding that makes
it undesirable for the patient to participate in the study
15. Other co-existing malignancies or malignancies diagnosed within the last 5 years
with the exception of basal cell carcinoma or cervical cancer in situ
16. Life expectancy of less than 12 weeks
17. Treatment with a non-approved or investigational drug within 30 days before Day 1
of study treatment
18. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site)
19. Previous enrolment or treatment in the present study.

1. Conosciuta severa ipersensibilità a gefitinib o a qualche eccipiente del prodotto.
2. Trattamento precedente con inibitori tirosinchinasici dell’EGFR eccetto gefitinib seguito da conseguente trattamento anti-tumorale (includendo la chemioterapia ed escludendo inibitori tirosinchinasici dell’EGFR. Una precedente chemioterapia adiuvante è permessa. Precedente chirurgia o radioterapia deve essere stata completata più di 6 mesi prima dell’inizio del trattamento di studio. La radioterapia palliativa deve essere completata almeno 4 settimane prima dell’inizio del trattamento di studio con tossicità alle radiazioni non persistente. Progressione di malattia o malattia stabile (SD) <12 settimane come migliore risposta al primo trattamento con gefitinib.
3. Pazienti che richiedono radioterapia la polmone al momento dell’entrata nello studio o nel future prossimo.
4. Storia medica passata di malattia intersiziale del polmone, malattia intersiziale indotta da farmaco, malattia intersiziale, polmonite da radiazioni che richiede trattamento con steroidi o qualsiasi evidenza di malattia interstiziale del polmone clinicamente attiva.
5. Fibrosi polmonare idiopatica pre-esistente evidenziata da CT scan al baseline.
6. Insufficiente funzione polmonare come determinato da esame clinic o tensione di ossigeno arterioso (PaO2) < 70 Torr.
7. Conosciute o sospette metastasi cerebrali o compression alla colonna vertebrale, a meno che non trattate con chirurgia e/o radiazioni e stabili senza il trattamento con steroidi per almeno 4 settimane prima della prima dose del farmaco di studio.
8. Qualsiasi tossicità cronica non risolta di grado CTC >2 dalla precedente terapia anti-tumorale.
9. Uso concomitatnte di induttori conosciuti del CYP 3A4 come fenitoina, carbamazepina, rifampicina, barbiturici e Erba di San Giovanni.
10. Donne in gravidanza o in allattamento
11. A giudizio degli sperimentatori, qualsiasi evidenza di malattia sistemica severa o non controllata (es. malattie respiratorie, cardiache, epatiche o renali instabili o non compensate).
12. Evidenza di quasiasi altro disordine clinic o esame di laboratorio che rende inadatta la partecipazione del paziente allo studio
13. Altri tumori maligni coesistenti o diagnosticati negli ultimo 5 anni, ad eccezione del carcinoma cellular basale o del tumore cervical in situ.
14. Aspettativa di vita di meno di 12 settimane.
15. Trattamento con un farmaco sperimentale non approvato nei 30 giorni precedenti l’inizio dell’assunzione del farmaco in studio.
16. Coinvolgimento nella pianificazione e/o conduzione dello studio (si applica sia allo staff AstraZeneca sia allo staff del centro sperimentale).
17. Precedente arruolamento o trattamento in questo studio.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

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

E.8.1.1

Randomised