Clinical Trial Results:
Phase II, Open Label, Single Arm Study Assessing the Clinical Benefit of SAR125844, Administered as Single Agent by Weekly Intravenous (IV) Infusion, for the Treatment of Patients With Advanced Pretreated Non-Small Cell Lung Cancer (NSCLC) Harboring MET Gene Amplification
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Summary
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EudraCT number |
2014-005696-93 |
Trial protocol |
BE HU DE ES NL CZ GR FR AT PL IT |
Global end of trial date |
05 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Jan 2017
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First version publication date |
05 Jan 2017
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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 |
ACT14205
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02435121 | ||
WHO universal trial number (UTN) |
U1111-1163-1136 | ||
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Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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 |
23 Feb 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 |
05 Jan 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the objective response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 reviewed by an Independent Third Party Review, of SAR125844 in subjects with advanced pretreated NSCLC harboring MET gene amplification.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency.
Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Nov 2015
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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 |
Belgium: 1
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Worldwide total number of subjects |
1
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EEA total number of subjects |
1
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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) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 1 site in Belgium from 09 November 2015 to 05 January 2016. | ||||||||
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Pre-assignment
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Screening details |
Out of 153 subjects pre-screened, only 1 subject was enrolled and treated in the study. This subject discontinued due to disease progression (DP) and considered as completed (as per protocol). | ||||||||
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Period 1
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Period 1 title |
Overall Study (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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SAR125844 | ||||||||
Arm description |
SAR125844 570 mg/m^2 intravenous (IV) infusion over 3 hours once weekly in each cycle (each cycle of 3 weeks) until unacceptable toxicity, DP, or consent withdrawal. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
SAR125844
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
SAR125844 570 mg/m^2 once weekly.
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Baseline characteristics reporting groups
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Reporting group title |
SAR125844
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Reporting group description |
SAR125844 570 mg/m^2 intravenous (IV) infusion over 3 hours once weekly in each cycle (each cycle of 3 weeks) until unacceptable toxicity, DP, or consent withdrawal. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SAR125844
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Reporting group description |
SAR125844 570 mg/m^2 intravenous (IV) infusion over 3 hours once weekly in each cycle (each cycle of 3 weeks) until unacceptable toxicity, DP, or consent withdrawal. | ||
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End point title |
Percentage of Subjects With Objective Response [1] | ||||||||
End point description |
Objective response rate was defined as the percentage of subjects from the assessed population with complete response (CR) or partial response (PR) according to the RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. An objective response was confirmed at least 4 weeks after the first documentation of response.
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End point type |
Primary
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End point timeframe |
Baseline up to DP, death or study cut-off, whichever came first (maximum duration: 58 days)
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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: Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| Notes [2] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of response (DOR) | ||||||||
End point description |
DOR was defined as the time (in weeks) from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of DP or death (due to any cause), whichever occurred first. In the absence of DP or death, the DOR should be censored at the date of the last tumor assessment or the cutoff date, whichever occurs first.
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End point type |
Secondary
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End point timeframe |
From the time of the first documented evidence of a confirmed CR or PR until DP, death or study cut-off, whichever came first (maximum duration: 58 days)
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| Notes [3] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-Free Survival (PFS) | ||||||||
End point description |
PFS was defined as time interval (in months) between the date of the first infusion of SAR125844 to the date of first documentation of tumor progression or death due to any cause, whichever occurs first. In the absence of DP or death, the subject was to be censored at the date of the last tumor assessment or the cut-off date, whichever occurs first. DP was defined using RECIST version 1.1 as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
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End point type |
Secondary
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End point timeframe |
Baseline up to DP, death or study cut-off, whichever came first (maximum duration: 58 days)
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| Notes [4] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival (OS) | ||||||||
End point description |
OS was defined as the time interval (in months) from the date of first infusion of SAR125844 to the date of death due to any cause. In the absence of death, the subject was to be censored at the last date the subject was known to be alive or the analysis cut-off date if the subject was known to be alive after analysis cut-off date.
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End point type |
Secondary
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End point timeframe |
Baseline up to death or study cut-off date, whichever came first (maximum duration: 58 days)
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| Notes [5] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax) for SAR125844 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1: 5 minutes before the end of infusion (EOI), 15 minutes, 1 hour, 2.5 to 3 hours, 4 hours and 45 hours after EOI
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| Notes [6] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve (AUC) for SAR125844 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1: 5 minutes before EOI, 15 minutes, 1 hour, 2.5 to 3 hours, 4 hours and 45 hours after EOI
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| Notes [7] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Clearance (CL) for SAR125844 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1: 5 minutes before EOI, 15 minutes, 1 hour, 2.5 to 3 hours, 4 hours and 45 hours after EOI
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| Notes [8] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of Distribution at Steady State (Vss) for SAR125844 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1: 5 minutes before EOI, 15 minutes, 1 hour, 2.5 to 3 hours, 4 hours and 45 hours after EOI
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| Notes [9] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Reach Maximum Observed Plasma Concentration (Tmax) for SAR125844 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1: 5 minutes before EOI, 15 minutes, 1 hour, 2.5 to 3 hours, 4 hours and 45 hours after EOI
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| Notes [10] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) at Day 1 of Each Cycle and at End of Treatment (EOT) | ||||||||
End point description |
The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer subjects. It includes five functional scales (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms scales (fatigue, pain, nausea/vomiting) and other single items (dyspnea, appetite loss, constipation, insomnia, diarrhoea and financial difficulties). 28 questions used 4 point scale (1 “Not at all” to 4 “Very much”); 2 questions used 7-point scale (1 “Very poor” to 7 “Excellent”). Scores were averaged and transformed to 0-100 scale; higher scores indicated better level of functioning or greater degree of symptoms.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Cycle 1), then Day 1 of each cycle (before SAR125844 administration) and at EOT (30 days after last dose) (maximum duration: 58 days)
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| Notes [11] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Score at Day 1 of Each Cycle and at EOT | ||||||||
End point description |
QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Response ranges from 1 “not at all” to 4 “very much”. Scores for each item were transformed to 0 to 100 , where higher symptom score = greater degree of symptoms.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Cycle 1), then Day 1 of each cycle (before SAR125844 administration) and at EOT (30 days after last dose) (maximum duration: 58 days)
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| Notes [12] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Cancer Therapy Satisfaction Questionnaire (CTSQ) Score at Day 1 of Cycle 4 and at EOT | ||||||||
End point description |
CTSQ is a validated 16-item questionnaire that measures three domains related to subject’s satisfaction with cancer therapy. These include expectations of therapy (5 questions), feelings about side effects (4 questions), and satisfaction with therapy (7 questions). All questions were assessed on a 5-point scale; 1=never to 5=always. Scores from all questions were averaged and transformed to provide a total score range of 0-100; where higher scores represent better health.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Cycle 1), then Day 1 of Cycle 4 (before SAR125844 administration) and at EOT (30 days after last dose) (maximum duration: 58 days)
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| Notes [13] - Endpoint was not analyzed as study terminated prematurely due to unsatisfactory subject recruitment. |
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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 |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (58 days) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported AEs are treatment emergent that is AEs that developed/worsened that occurred during 'the treatment emergent period’ (time from first dose of study drug until 30 days after the last administration of study drug).
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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 |
18.1
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Reporting groups
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Reporting group title |
SAR125844
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Reporting group description |
SAR125844 570 mg/m^2 IV infusion over 3 hours once weekly in each cycle (each cycle of 3 weeks) until unacceptable toxicity, DP, or consent withdrawal. | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 of the endpoints were analysed as the study was terminated prematurely due to unsatisfactory subject recruitment. | |||||||
