Lung Cancer
Conditions
Brief 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
Detailed 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
Interventions
DRUGGefitinib 250mg
Gefitinib 250mg once daily
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 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) | 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 |
| Clinical Benefit Rate | 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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) | 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. |
| Overall Survival (OS) | 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) | 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. |
| Treatment Duration With Gefitinib | 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) | Treatment duration was calculated from the date of the first to the date of the last intake. |
| Time to Worsening of Disease Related Symptoms | 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) | 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. |
Countries
Italy
Participant flow
Recruitment details
Overall, 61 patients were enrolled from July 2012 to July 2014 from 25 medical clinics across Italy: of these, 59 received gefitinib.
Pre-assignment details
The study foresees a screening period of 28 days where the investigator had to obtain signed informed consent from the potential patient before any study specific procedures are performed, and determine patient eligibility. At the end of the screening period the patient started the treatment with gefitinib
Participants by arm
| Arm | Count |
|---|---|
| Gefitinib 250 mg/die, oral | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Progressive disease | 47 |
| Overall Study | unknown reason | 1 |
Baseline characteristics
| Characteristic | Gefitinib |
|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized White | 61 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 58 |
| serious Total, serious adverse events | 10 / 58 |
Outcome results
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
Time frame: 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)
Population: CBR was analyzed both on FAS and EFS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefitinib | Clinical Benefit Rate | 32 Patients |
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
Time frame: 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)
Population: Analysis performed both in the FAS population (i.e. all enrolled patients into the study) and in EFS population (i.e. all screened patients who entered and received at least one dose of study agent)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefitinib | Objective Response Rate | 3 Patients |
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.
Time frame: 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)
Population: Analysis conducted both in FAS and EFS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib | Overall Survival (OS) | 311 days |
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.
Time frame: 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)
Population: PFS was analysed on FAS and EFS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib | Progression Free Survival | 84 Days |
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.
Time frame: 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)
Population: Analysis performed on EFS \& FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib | Time to Worsening of Disease Related Symptoms | 93 days |
Secondary
Treatment Duration With Gefitinib
Treatment duration was calculated from the date of the first to the date of the last intake.
Time frame: 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)
Population: Analysis performed on EFS \& FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib | Treatment Duration With Gefitinib | 108 days |