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

Lung Cancer Clinical Trial

— ICARUS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01530334
• Other study ID #: D7913L00138
• Secondary ID: EUDRACT n 2011-0
• Status: Completed
• Phase: Phase 2
• First received: January 31, 2012
• Last updated: January 26, 2016
• Start date: July 2012
• Est. completion date: July 2014

Study information

• Verified date: January 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 130 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer

Intervention

Drug:
• Gefitinib 250mg
Gefitinib 250mg once daily

Locations

Country	Name	City	State
Italy	Research Site	Alessandria
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Cona
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Lecce
Italy	Research Site	Macerata
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Napoli
Italy	Research Site	Novara
Italy	Research Site	Parma
Italy	Research Site	Perugia
Italy	Research Site	Pordenone
Italy	Research Site	Ravenna
Italy	Research Site	Rimini
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Torino
Italy	Research Site	Treviso
Italy	Research Site	Udine
Italy	Research Site	Verona

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No