Clinical Trial Results:
Phase II Study of ADI-PEG 20 in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer
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Summary
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EudraCT number |
2009-017885-22 |
Trial protocol |
BE DE GB |
Global end of trial date |
15 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2020
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First version publication date |
29 Mar 2020
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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 |
LUD2009-007
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01266018 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ludwig Institute for Cancer Research
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Sponsor organisation address |
666 3rd Ave, New York, United States, 10017-4011
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Public contact |
Clinical Trial Information, Ludwig Institute for Cancer Research, 001 2124501515, clintrialinformation@licr.org
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Scientific contact |
Clinical Trial Information, Ludwig Institute for Cancer Research, 001 2124501515, clintrialinformation@licr.org
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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 |
19 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Jun 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jul 2013
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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 |
The primary objective of this study was to assess the clinical efficacy of ADI-PEG 20, via the
primary endpoint of tumor response by RECIST, in subjects with relapsed
sensitive or refractory Small Cell Lung Cancer (SCLC).
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Protection of trial subjects |
The study was conducted in full conformity with the current revision of the Declaration of
Helsinki, International Conference on Harmonisation (ICH) Guidelines and applicable local laws and
regulations, with the understanding that local laws and regulations took precedence over respective
sections in the Declaration of Helsinki and/or the ICH Guidelines. Before study drug could be
shipped and subjects could be entered into the study, the Institutional Review Board (IRB) or its
equivalent must have approved the protocol and informed consent form in writing.
The investigator was to obtain witnessed written informed consent from each subject or the
subject’s legally authorized representative after adequate explanation of the aims, methods,
anticipated benefits, and potential hazards of the study and before any study procedures were
performed. Subjects were only to be identified by their initials, date of birth, and subject
number on the case report forms (CRFs) or other documents submitted
to the Sponsor.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jan 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 |
United Kingdom: 3
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
United States: 11
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Country: Number of subjects enrolled |
Taiwan: 6
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Worldwide total number of subjects |
22
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EEA total number of subjects |
5
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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) |
14
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
This was a 2-arm, open-label, phase 2 study of pegylated arginine deiminase (ADI-PEG) 20 in subjects with relapsed sensitive or refractory small cell lung cancer (SCLC). ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m^2 once weekly for a 4-week cycle. | |||||||||||||||
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Pre-assignment
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Screening details |
22 subjects were enrolled in the study and were treated. | |||||||||||||||
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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 | |||||||||||||||
Blinding implementation details |
none
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1 Sensitive Disease | |||||||||||||||
Arm description |
Cohort 1 comprised subjects with "sensitive" disease, defined as subjects who were treated with 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
ADI-PEG 20
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Investigational medicinal product code |
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Other name |
Arginine deiminase pegylated
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m^2 (36.8 mg/m^2) once weekly for 4 weeks followed by a 1-week follow-up (1 cycle).
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Arm title
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Cohort 2 Refractory Disease | |||||||||||||||
Arm description |
Cohort 2 comprised subjects with “refractory” disease, defined as subjects who either (a) were treated with 1 previous line of chemotherapy and either had no response or progressed < 90 days after completing treatment or (b) required third-line therapy, i.e., had completed 2 previous lines of chemotherapy, regardless of response. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
ADI-PEG 20
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Investigational medicinal product code |
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Other name |
Arginine deiminase pegylated
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m^2 (36.8 mg/m^2) once weekly for 4 weeks followed by a 1-week follow-up (1 cycle).
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Baseline characteristics reporting groups
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Reporting group title |
overall study
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Reporting group description |
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End points reporting groups
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Reporting group title |
Cohort 1 Sensitive Disease
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Reporting group description |
Cohort 1 comprised subjects with "sensitive" disease, defined as subjects who were treated with 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle. | ||
Reporting group title |
Cohort 2 Refractory Disease
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Reporting group description |
Cohort 2 comprised subjects with “refractory” disease, defined as subjects who either (a) were treated with 1 previous line of chemotherapy and either had no response or progressed < 90 days after completing treatment or (b) required third-line therapy, i.e., had completed 2 previous lines of chemotherapy, regardless of response. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle. | ||
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End point title |
Best overall response [1] | |||||||||||||||
End point description |
Tumor responses were evaluated using any appropriate imaging type and were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per RECIST for target lesions and assessed by MRI:
Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
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End point type |
Primary
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End point timeframe |
Every 4 to 8 weeks for up to 16 weeks
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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: Because no subject in the refractory disease cohort had a response, the study was terminated early and declared negative. |
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| Notes [2] - includes all subjects who were evaluable for tumor response [3] - Includes all subjects who were evaluable for tumor response |
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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 (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent.
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Adverse event reporting additional description |
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome.
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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 |
13.1
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Reporting groups
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Reporting group title |
All Subjects (Safety Analysis Set)
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Reporting group description |
Includes all subjects in Cohort 1 (n = 9) and Cohort 2 (n = 13) who received at least 1 dose of study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
