An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First line Treatment in Caucasian Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) - IRESSA PhIV IFUM

• Register: EUCTR
• Last refreshed on: 15 July 2013
• Main ID: EUCTR2010-018614-70-BG
• Date of registration: 27/05/2011
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First line Treatment in Caucasian Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) - IRESSA PhIV IFUM
• Scientific title: An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First line Treatment in Caucasian Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) - IRESSA PhIV IFUM
• Date of first enrolment: 07/07/2011
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018614-70
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Single Arm If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Bulgaria, France, Greece, Hungary, Italy, Norway, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria at screening, at enrolment (Visit 1) and at Start of Study Treatment (Visit 2):
1. Provision of informed consent prior to any study specific procedures
2. Caucasian female or male patients aged 18 years or over, eligible for standard first line treatment for NSCLC
3. Histologically confirmed NSCLC: adenocarcinoma, including Bronchoalveolar Carcinoma (BAC), squamous cell carcinoma, large cell carcinoma, adenosquamous carcinoma or undifferentiated carcinoma. Cytological confirmation alone is NOT acceptable
4. Locally advanced stage IIIA/B not suitable for curative intent therapy or stage IV disease
5. 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
6. WHO performance status 0-2
Inclusion criterion at enrolment (Visit 1) and at Start of Study Treatment (Visit 2)
7. NSCLC with an activating sensitising EGFR TK mutation as determined by using a well-validated and robust methodology (also see exclusion criterion 5 below).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion criteria at screening , at enrolment (Visit 1) and at Start of Study Treatment (Visits 2):
1. Known severe hypersensitivity to gefitinib or any of the excipients of the product
2. Prior chemotherapy or other systemic anti-cancer treatment (including EGFR TKIs). Previous adjuvant chemotherapy is allowed, if completed more than 6 months prior to starting study treatment. 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. Patient considered to require radiotherapy to the lung at the time of study entry or in the near future
4. 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
5. Presence EGFR TK mutation reported to confer resistance to EGFR TKI: i.e. exon 20 point mutation (T790M or S768I EGFR) or exon 20 insertion as determined by using a well-validated and robust methodology. See Appendix I for mutations eligible for this study
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-exisiting 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. Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy
10. Concomitant use of known CYP 3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort
11. Pregnancy or breast-feeding
12. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
13. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
14. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
15. Life expectancy of less than 12 weeks
16. Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment
17. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
18. Previous enrolment or treatment in the present study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non Small Cell Lung Cancer.
MedDRA version: 15.0 Level: LLT Classification code 10025053 Term: Lung cancer non-small cell stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 15.0 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 15.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: IRESSA
Product Name: Gefitinib
Product Code: AZD1839
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GEFITINIB
CAS Number: 184475-35-2
Current Sponsor code: ZD1839
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Main Objective: To evaluate the objective response rate (ORR; confirmed complete response(CR) or partial response (PR)) of gefitinib using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in Caucasian patients with EGFR M+ NSCLC (activating sensitising Epidermal Growth Factor Receptor EGFR mutation postive (EGFR M+))

Primary end point(s): The primary objective of this study is to evaluate the objective response rate (ORR; confirmed complete response (CR) or partial response (PR)) of gefitinib using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in Caucasian patients with activating sensitising Epidermal Growth Factor mutation positive (EGFR M+) NSCLC.

Secondary Objective: The secondary objectives of the study are:
· To evaluate disease control rate, progression free survival and overall survival in Caucasian patients with EGFR M+ NSCLC
· To evaluate the safety profile of gefitinib in Caucasian patients with EGFR M+ NSCLC
· To define the correlation between clinical characteristics and baseline tumour EGFR mutation status in the screened NSCLC population
· To characterise the pharmacokinetics of gefitinib taking into account demographic and clinical covariates in Caucasian patients with EGFR M+ NSCLC.

Secondary ID(s)

2010-018614-70-PT

D791AC00014