Clinical Trial Results:
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
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Summary
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EudraCT number |
2011-005157-31 |
Trial protocol |
IT |
Global end of trial date |
09 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jun 2016
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First version publication date |
23 Jun 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D7913L00138
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
AstraZeneca SpA
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Sponsor organisation address |
Via Sforza 5, Milan, Italy, 20080
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Public contact |
Elisa Pastore, AstraZeneca SpA, +39 0298011,
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Scientific contact |
Silvia Ferrari, AstraZeneca SpA, +39 0298015227, silvia.ferrari@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Feb 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jan 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jan 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to describe Objective response rate (ORR; confirmed complete response (CR) or partial response (PR) as per the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and the disease control rate (CBR; confirmed complete response (CR) or partial response (PR) or stable disease (SD)) of gefitinib using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in patients diagnosed for activating sensitising Epidermal Growth Factor mutation positive (EGFR M+) NSCLC.
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Protection of trial subjects |
The Informed Consent Forms was incorporated wording that complies with relevant data protection and privacy legislation. Pursuant to this wording, patients authorised the collection, use and disclosure of their study data by the investigator and by those persons who need that information for the purposes of the study. The Master Informed Consent Forms explained that study data were stored in a computer database, maintaining confidentiality in accordance with national data legislation. All data computer processed by AstraZeneca were identified by “E-code”, and study code. AstraZeneca did not provide individual genotype results to patients, any insurance company, any employer, their family members, general physician or any other third party, unless required to do so by the law. Extra precautions were taken to preserve confidentiality and prevent study data being linked to the identity of the patient. In exceptional circumstances, however, certain individuals might see both the study data and the personal identifiers of a patient. For example, in the case of a medical emergency, an AstraZeneca Physician or an investigator might know a patient’s identity and also have access to his or her study data. Also Regulatory authorities may require access to the relevant files.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
18 Jul 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 61
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Worldwide total number of subjects |
61
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EEA total number of subjects |
61
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
21
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From 65 to 84 years |
39
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
Investigator had to obtain signed informed consent from the potential patient before any study specific procedures are performed. He/she determined patient eligibility and assigned potential patient with a unique identification number. He/she recorded enrolment date for patients who were eligible for the study in the eCRF at screening Visit. | ||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
61 | ||||||||||||
Number of subjects completed |
61 | ||||||||||||
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Period 1
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Period 1 title |
Baseline period
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Gefitinib | ||||||||||||
Arm description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Gefitinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Gefitinib 250 mg in oral tablet form will be administered once daily.
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Period 2
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Period 2 title |
Open label phase
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Is this the baseline period? |
No | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Gefitinib | ||||||||||||
Arm description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Gefitinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Gefitinib 250 mg in oral tablet form will be administered once daily.
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Baseline characteristics reporting groups
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Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Gefitinib
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All enrolled patients
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End points reporting groups
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Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||
Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||
Subject analysis set title |
Gefitinib
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All enrolled patients
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End point title |
Objective Response Rate [1] | ||||||||||||
End point description |
ORR is the sum of CR and PR
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End point type |
Primary
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End point timeframe |
Overall Study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. |
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| Notes [2] - 3 patients with a response [3] - 3 patients with a response |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Clinical Benefit Rate [4] | ||||||||||||
End point description |
CBR is the sum of CR, PR and SD
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End point type |
Primary
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End point timeframe |
Overall Study
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Analysis of ORR and CBR was based on frequency analysis (n,%) and 95% CI. I tried to add this info the form "Statsitical analysis" but an additional error appear. The system required the results of a group comparison. The study was a single arm trial. |
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| Notes [5] - 32 patients with CBR [6] - 32 patients with CBR |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression Free Survival | ||||||||
End point description |
PFS was calculated as the time from the first dose of gefitinib study treatment until the date of (i) objective disease progression as defined by RECIST 1.1 or (ii) death from any cause in the absence of progression.
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End point type |
Secondary
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End point timeframe |
Overall Study
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
OS was calculated as the time from the first dose of gefitinib study treatment until the date 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 recorded date on which the patient was known to be alive.
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End point type |
Secondary
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End point timeframe |
Overall Study
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| No statistical analyses for this end point | |||||||||
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End point title |
Treatment duration with gefitinib | ||||||||||||
End point description |
Treatment duration will be calculated from the date of first trial therapy intake to the date of last trial therapy taken.
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End point type |
Secondary
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End point timeframe |
Overall Study
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to worsening of disease related symptoms | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Overall Study
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| Notes [7] - Max score on FACT-L is 136.Worsening is defined as a change from baseline in total score <= -6 |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are those with start date beyond or equal to the informed consent date.
Analysis includes adverse events with starting date until 30 days after the last study drug dose intake.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg in oral tablet form administered once daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Jun 2013 |
At the previous text on measurable disease defined as at least one lesion, preferentially 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 was added that in the presence of only 1 lesion previously irradiated, this can be accepted if a progression of disease has been documented compared with the previous assessment or if the physician considers the modifications of the lesion worthy of a new treatment. Exclusion criteria #9 was modified and steroids were admitted if the purpose of their use was antiedemigenous prophylaxis, in absence of neurological symptoms. Total sample was reduced from 92 pateints to 54 evaluable patients. Statistical methods for analysis were better specified. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
