Clinical Trial Results:
Phase II trial of oral vinorelbine in Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) positive mutation after a failure to treatment with EGFR Tyrosine Kinase Inhibitors (TKI) in first line.
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Summary
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EudraCT number |
2012-003361-18 |
Trial protocol |
AT PL |
Global end of trial date |
17 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Feb 2019
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First version publication date |
20 Feb 2019
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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 |
PM0259CA229J1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Pierre Fabre Médicament
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Sponsor organisation address |
45 place Abel Gance, Boulogne, France, 92100
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Public contact |
Jean Claude Vedovato, PIERRE FABRE MEDICAMENT, +33 (0)534506870, jean.claude.vedovato@pierre-fabre.com
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Scientific contact |
Jean Claude Vedovato, PIERRE FABRE MEDICAMENT, +33 (0)534506870, jean.claude.vedovato@pierre-fabre.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 |
15 Jan 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Apr 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 |
To evaluate the disease control rate (CR, PR, SD) of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor.
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Protection of trial subjects |
The study was conducted according to Good Clinical Practice (GCP) (CPMP/ICH/135/95), the principles stated in the Declaration of Helsinki (1964) and its subsequent amendments thereto, and national regulations. The request for authorization by the Competent Authority or its notification (depending on National Regulations) was carried out by the Sponsor. The study protocol and related documents, including the informed consent forms (ICFs), were submitted for approval to independent, local or national Independent Ethics Committees (IECs) and to competent authorities (CAs) before the study set-up, according to national regulations.
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Background therapy |
Oral vinorelbine is a drug with moderate emetogenic risk (emetic risk: 30-90 %). Anti-emetic prophylaxis with oral 5-HT3 antagonists was recommended from the first cycle before each oral vinorelbine intake. The use of corticosteroids as antiemetic was also allowed. Patients had to receive full supportive care including antibiotics, anti-diarrhoeals, analgesics, transfusion of blood products, when appropriate. The use of drugs with laxative properties had to be avoided. | ||
Evidence for comparator |
No control arm was planned as the study aimed at evaluating the efficacy of oral vinorelbine as a proof of concept in this selected population of patients. | ||
Actual start date of recruitment |
01 Dec 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety, Ethical reason, Regulatory reason, Scientific research | ||
Long term follow-up duration |
2 Years | ||
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 |
Poland: 11
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Country: Number of subjects enrolled |
Italy: 11
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Country: Number of subjects enrolled |
Singapore: 8
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Worldwide total number of subjects |
30
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EEA total number of subjects |
22
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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) |
12
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From 65 to 84 years |
18
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was planned in a total of 55 patients with locally advanced or metastatic EGFR mutation positive NSCLC after failure to 1st line EGFR-TKI therapy and with at least 1 measurable disease . A 2nd cohort was opened to include patients with asymptomatic brain metastases incidentally found during screening process (no local treatment needed). | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Due to a slow recruitment, the Sponsor decided to halt permanently recruitment of patients into the study and terminate the study. Only a total of 30 patients were enrolled, all were eligible and received at least one dose of study treatment. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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ITT Population | ||||||||||||||||||||
Arm description |
A total of 30 patients were enrolled, all were eligible and received at least one dose of study treatment. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Vinorelbine
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Investigational medicinal product code |
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Other name |
Navelbine
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Oral Vinorelbine was given at 60mg/m2 weekly, for cycle 1, then 80 mg/ m2 weekly for subsequent cycles according to haematological tolerance (a cycle is a treatment period between 3 administrations of weekly oral vinorelbine on day 1, day 8 and day 15). The study treatment was to be continued at least 4 cycles unless documented disease progression, unacceptable toxicity or patient’s refusal. This treatment regimen is within the frame of the market authorization of oral Vinorelbine.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ITT Population
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Reporting group description |
A total of 30 patients were enrolled, all were eligible and received at least one dose of study treatment. | ||
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End point title |
Disease control rate (DCR) [1] | ||||||||
End point description |
DCR was defined as by Recist v1.1 (CR+PR+SD) rates in the ITT population (all registered and treated patients) with 95% CI calculated following the exact method. Overall, in the ITT population, two PR (N=2/30), one PR not confirmed (SD), and 16 SD were achieved, yielding a DCR of 63.3% [95%CI: 43.8-80.1].
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End point type |
Primary
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End point timeframe |
Tumor assessment was performed at baseline, then every 6 weeks according to RECIST v1.1 until progressive disease documented by the investigator.
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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 analysis has been specified because the studu is a single-arm study |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall response rate | ||||||||||||||||
End point description |
Overall Response rate (ORR) was defined as the sum of CR and PR (using the best confirmed response recorded from the date of randomisation to the end of treatment) in the ITT population. There were 2 confirmed PR (N=2/30), and 1 not confirmed PR, yielding an ORR of 6.7%.
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End point type |
Secondary
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End point timeframe |
Overall Response rate (ORR) was evaluated at specified timelines (every 6 weeks until the end of study) in the ITT population by the investigator.
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Duration of disease control | ||||||||
End point description |
The disease control rate (sum of confirmed CR, confirmed PR and stabilisation rate) was evaluated for the ITT population using Kaplan Meier curves and Confidence intervals on the median duration of disease control were calculated using the reflected method. Patients who were lost to follow-up without progression, or have reached the
time point of analysis without a known record of progression or death had the duration of disease control censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occured last. Patients who received a new anti-tumoral treatment, whatever the type of treatment, before their disease progression were censored at the start date of this new anti-tumoral treatment.
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End point type |
Secondary
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End point timeframe |
The duration of disease control (CR, PR and stabilization of at least 3 months) was measured from the date of registration until the criteria for disease progression is met or the date of death or start of new anticancer therapy.
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Attachments |
KM curve of the Duration of Disease Control |
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End point title |
Duration of stable disease | ||||||||
End point description |
The duration of stable disease was estimated on the ITT population using Kaplan Meier curves and Confidence intervals on the median were calculated using the reflected method. Patients who were lost to follow-up without progression, or reach the time point of analysis without a known record of progression or death had the duration of disease control censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last. Patients who received a new anti-tumoral treatment, whatever the type of treatment, before their disease progression were censored at the start date of this new anti-tumoral treatment.
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End point type |
Secondary
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End point timeframe |
The duration of stable disease was measured from the date of registration until the criteria for disease progression was met or the date of death (whatever the reason of of death) or start of new anticancer therapy.
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Attachments |
Kaplan Meier Stable disease |
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End point title |
Overall survival (OS) | ||||||||
End point description |
Analyses of Overall Survival were performed with the Kaplan-Meier method. At the time of data base lock, a total of 24/30 (80%) patients died, all due to disease progression, 4/30 (13.3%) patients were still alive and 2/30 (6.7) patients were lost to follow-up. Overall survival of patients lost to follow-up or without a known record of death was censored at the date of last news.
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End point type |
Secondary
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End point timeframe |
Overall survival was evaluated from the date of registration to the date of death due to any cause in the ITT population.
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Attachments |
Kaplan - Meier Survival time in months |
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Adverse events information
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Timeframe for reporting adverse events |
Each patient was assessed for occurrence of AEs throughout the study period. At the time of the database lock, all patients discontinued study treatment, 24/30 patients died due to disease progression, 4 patients were still alive and 2 were lost to FUP.
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Adverse event reporting additional description |
A total of 166 cycles were administered for a mean number of cycles of 5.5 (± 5.2), with one third (33.3%) of the patients having received at least 6 cycles of the study medication. Approximately one fifth (23.3%) of the patients received > 90% of the planned dose of oral vinorelbine. The median relative dose intensity was 77.6% [range:46.8-105.0].
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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 |
12.1
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3.3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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17 Jul 2013 |
Local requirement for performing pregnancy tests to all women of childbearing potential on a regular basis throughout the treatment period (every cycles)
Not implemented –Country abandoned (Refusal of study in Dec ,13 by ANMAT Competent Authorities)
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28 Mar 2014 |
Inclusion of patients with brain metastases (if asymptomatic and steroid free) in a new cohort of 55 patients
Wash out period of 2 weeks for patients previously treated with an approved EGFR-TKI in the frame of a clinical trial, instead of 4 weeks;
2 weeks interval from radiotherapy before starting with oral vinorelbine, instead of 4 weeks.
Prolongation of inclusion until Q1 2015
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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 | |||
