Iressa Re-Challenge in Advanced NSCLC EGFR M+ Patients Who Responded to Gefitinib USed as 1st Line or Previous Treatment

Study Overview
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Brief Summary
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the primary objective is 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

Detailed Description
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A phase II Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA�) as 3rd line 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 responded to gefitinib in 1st line and progressed after 2nd line chemotherapy

Official Title
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A Phase II Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA) as 3rd Line 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 Responded to Gefitinib in 1st Line and Progressed After 2nd Line Chemotherapy

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Gefitinib 250mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria at screening (Visit 1) and at Start of Study Treatment (Visit 2): Provision of informed consent prior to any study specific procedures. 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. 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. 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. WHO / ECOG / Zubrod performance status 0-2. Exclusion Criteria: 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. Progression disease or stable disease (SD) <12 weeks as best response to the 1st line treatment with gefitinib Not progressing during or after the last anti-cancer treatment. Considered to require radiotherapy to the lung at the time of study entry or in the near future 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 Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline Insufficient lung function as determined by either clinical examination or an arterial oxygen tension (PaO2) of < 70 Torr 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 Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy Concomitant use of known CYP 3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort Pregnancy or breast-feeding As judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg, unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ Life expectancy of less than 12 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: open label single arm with Gefitinib 250MG once daily<br>Gefitinib 250 mg/day open label until progression disease / toxicity / consent withdrawal | Drug: Gefitinib 250mg<br>* Gefitinib 250mg once daily<br>* Other names: Iressa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective Response Rate is the sum of Complete response (CR) and Partial Response (PR) response. Evaluated by recist criteria v 1.1., for target lesions and assesed by CT or MRI: Complete Response (CR), Disapperance of all target lesions; Partial Response (PR),>=30% decrease in the sum of longest diamteter of target lesions; Objective response rate (RR)=CR+PR | every 6 weeks after the Start of Study Treatment until objective disease progression or time of data cut off (6 months after the last patient has started study treatment) | 
| Clinical Benefit Rate | Clinical benefit rate is the sum of patients with a best visit response of Complete Response, Partial Response or Stable Desease Objective Response Rate is the sum of Complete response (CR) and Partial Response (PR) response. Evaluated by recist criteria v 1.1., for target lesions and assesed by CT or MRI: Complete Response (CR), Disapperance of all target lesions; Partial Response (PR),>=30% decrease in the sum of longest diamteter of target lesions, Stable Desease (SD) defined as no progression for>= 6 weeks. Objective response rate (RR)=CR+PR | every 6 weeks after the Start of Study Treatment until objective disease progression or time of data cut off (6 months after the last patient has started study treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free Survival was calculated as the time from the first dose of gefitinib study treatment until the date of (i) progression or (ii) death from any cause in the absence of progression. | every 6 weeks after the Start of Study Treatment until objective disease progression or time of data cut off (6 months after the last patient has started study treatment) | 
| Overall Survival (OS) | OS was calculated as the time from the first dose until the day of death from any cause. Any patient not known to have died at the time of data analysis was censored at the time of the last follow-up date. | every 6 weeks after the Start of Study Treatment until death or time of data cut off (6 months after the last patient has started study treatment) | 
| Treatment Duration With Gefitinib | Treatment duration was calculated from the date of the first to the date of the last intake. | every 6 weeks after the Start of Study Treatment until discontinuation of drug or time of data cut off (6 months after the last patient has started study treatment) | 
| Time to Worsening of Disease Related Symptoms | Time to worsening of disease related symptoms (LCS) Time to worsening of disease-related symptoms based on FACT-L LCS was defined as the interval from the date of enrollment to the first visit response of 'worsened' without a subsequent response of 'improved' or 'no change' within 21 days (or to the last assessment), death due to any cause, or early discontinuation from the study. Time to worsening was censored at the last non-missing assessment visit if the worsening was not observed. | every 6 weeks after the Start of Study Treatment until the worsening of desease related symptoms or time of data cut off (6 months after the last patient has started study treatment) |