Clinical Trial Results:
NGR012: A phase II study of NGR-hTNF administered in combination with doxorubicin every 3 weeks in patients affected by advanced or metastatic ovarian cancer
|
Summary
|
|
EudraCT number |
2007-000004-33 |
Trial protocol |
IT |
Global end of trial date |
17 Dec 2015
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
26 Jan 2020
|
First version publication date |
26 Jan 2020
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
NGR012
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
MolMed S.p.A.
|
||
Sponsor organisation address |
Via Olgettina, 58, Milan, Italy, 20132
|
||
Public contact |
MolMed S.p.A., Clinical Development, 0039 0221277234, clinical.operations@molmed.com
|
||
Scientific contact |
MolMed S.p.A., Clinical Development, 0039 0221277234, clinical.operations@molmed.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Dec 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Dec 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Antitumor activity defined as response rate according to RECIST criteria
|
||
Protection of trial subjects |
The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The study was performed in compliance with Good Clinical Practices (CPMP/ICH/135/95), and the essential documents are archived as required by the applicable regulatory requirements. The study and any amendments were reviewed by an Independent Ethics Committees or Institutional Review Boards.
|
||
Background therapy |
Patients affected by advanced or metastatic ovarian cancer previously treated with platinum regimens (cis or carboplatin) plus paclitaxel and with documented progression disease within 6 months from last chemotherapy administered (refractory/resistant population) or in progression disease after 6 months from last chemotherapy (platinum regimens plus paclitaxel) administered. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2008
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Italy: 37
|
||
Worldwide total number of subjects |
37
|
||
EEA total number of subjects |
37
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
17
|
||
From 65 to 84 years |
20
|
||
85 years and over |
0
|
||
|
|||||||||||||||
|
Recruitment
|
|||||||||||||||
Recruitment details |
Study period: First patient enrolled: 01 December 2008; Last patient completed: 17 December 2015; Study centres: 2 investigational study sites in Italy. | ||||||||||||||
|
Pre-assignment
|
|||||||||||||||
Screening details |
Totally 37 consented and screened patients received at least one dose of study medication and were included in the Safety population (SAF set). | ||||||||||||||
|
Period 1
|
|||||||||||||||
Period 1 title |
Overall period
|
||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
|
Arms
|
|||||||||||||||
|
Arm title
|
NGR-hTNF + doxorubicin | ||||||||||||||
Arm description |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
NGR-hTNF
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||
Dosage and administration details |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an
objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed.
|
||||||||||||||
Investigational medicinal product name |
Doxorubicin
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||
Dosage and administration details |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed.
|
||||||||||||||
|
|||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NGR-hTNF + doxorubicin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
NGR-hTNF + doxorubicin
|
||
Reporting group description |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed. | ||
|
|||||||||
End point title |
Response rate (RR) [1] | ||||||||
End point description |
The primary endpoint of the study was antitumor activity defined as response rate according to RECIST criteria. Response rate was defined as the percentage of patients having as best response throughout the study a CR or a PR: (CR + PR)/n. of patients in ENR population.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
The response rate was measured during the whole study.
|
||||||||
| 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: The study was conducted using Simon’s two-stage design method for the primary efficacy end point. Since 7 responses (complete or partial) were observed among the 37 patients, the study was to be considered to have a positive result. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression-free survival (PFS) | ||||||||
End point description |
Progression-free survival (PFS), defined as the time from baseline CT-scan date until the first observation of disease progression, or death due to any cause, or the last date the patient was known to be progression free or alive.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Progression-free survival (PFS) was measured during the whole study/at each cycle.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
Overall Survival (OS), defined as the time from baseline until the date of death from any cause or the last date the patient was known to be alive.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Patiens were followed for survival after documented disease progression or after discontinuation before disease progression (every 12 weeks)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Tumor marker CA125 detection | ||||||||
End point description |
Changes from baseline of tumor marker CA125.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
The level of tumor marker CA125 was measured before the treatment (within 14 days prior treatment) and during the treatment (every 2 cycles).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All adverse events and serious adverse events occurring after initiation of trial treatment will be recorded for 28 days after completion of the last treatment cycle. All serious adverse events related to the study drug will be recorded indefinitely.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NGR-hTNF + doxorubicin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients received 60 minutes intravenous NGR-hTNF infusion every 3 weeks at dose of 0.8 μg/m2 before of a dose of doxorubicin 60 mg/m2 as 15 minutes infusion. At reaching of a cumulative dose of doxorubicin of 550 mg/m2, a continuation of treatment (if patient was showing an objective response or is in stable disease) with single agent NGR-hTNF at dose of 0.8 μg/m2 every 3 weeks was allowed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
05 May 2008 |
Summary of changes:
- The reference name of the sponsor was changed;
- The introduction was modified according to the availability of results of new studies;
- The production process of the study drug has been changed, and therefore the protocol has been modified for the sections regarding pharmaceutical form, labelling, mode of dispensing and returning, and other details on study drug;
- Plan of visits schedule of assessments has been changed;
- Criteria for evaluation of relationship of adverse events have been modified;
- Other minor changes. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
