Clinical Trial Results:
Randomised, phase III multicenter, open study of lanreotide in non metastatic castration-resistant prostate cancer patients presenting elevated Chromogranin A levels
Summary
|
|
EudraCT number |
2010-019862-10 |
Trial protocol |
IT |
Global end of trial date |
25 Jun 2013
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
27 Feb 2016
|
First version publication date |
12 Aug 2015
|
Other versions |
v1 (removed from public view) |
Version creation reason |
|
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 |
A 93-52030-738
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01313273 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Ipsen
|
||
Sponsor organisation address |
Via Del Bosco Rinnovato, 6, Assago - Milano, Italy, 20090
|
||
Public contact |
Medical Director, Oncology, Ipsen, clinical.trials@ipsen.com
|
||
Scientific contact |
Medical Director, Oncology, Ipsen, clinical.trials@ipsen.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 |
01 Sep 2012
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
01 Sep 2012
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
25 Jun 2013
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To assess the efficacy in terms of Progression-free survival (PFS) of the administration of non steroidal anti androgens and LHRH-a (Arm A) versus lanreotide in addition to non steroidal anti androgens and LHRH-a (Arm B) as second line approach in non metastatic prostate cancer patients with castrate resistant disease and elevated CgA circulating levels. According to the updated guidelines of the PCWG2 Progression-free survival (PFS) will be considered a composite end point defined as the time from random assignment to disease progression in bone or soft-tissue, symptoms, or death.A rising PSA alone will not be considered an indicator of disease progression since radiographic or symptomatic progression better reflect changes in clinical status.Subjects stopping the study for any reason, including isolated PSA increase, will be censored at their last date of evaluation.Patients without tumor progression or death at the time of analysis will be censored at their last date of evaluation
|
||
Protection of trial subjects |
The Sponsor is responsible for monitoring this data to verify that the rights and well being of subjects are protected and that the trial is conducted in compliance with the protocol, GCP and regulatory requirements.
Lanreotide has been proven to be effective in reducing plasma CgA levels. All those evidence, support exploring the antineoplastic activity and efficacy of lanreotide in patients with progressive disease to first line hormonal treatment and eligible for second line hormone therapy (castration resistant patients) .
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jun 2011
|
||
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: 3
|
||
Worldwide total number of subjects |
3
|
||
EEA total number of subjects |
3
|
||
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) |
2
|
||
From 65 to 84 years |
1
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
Subjects ≥18 years meeting inclusion criteria were recruited for this study. | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
Investigators screened 8 subjects. Randomized 3 subjects and 5 were not randomized. | |||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Arm A : Non-steroidal Anti Androgens + LHRH-a | |||||||||||||||||||||
Arm description |
Non-steroidal anti androgens (e.g. bicalutamide 50 mg/day) plus Luteinizing Hormone-Releasing Hormone Analogues (LHRH-a) (e.g. triptorelin 3.75 mg/month) till progression. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Second line hormonal treatment
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||
Routes of administration |
Submucosal use
|
|||||||||||||||||||||
Dosage and administration details |
Luteinizing hormone-releasing hormone analogues (LHRH-a) ± Anti androgen were administered until the date of disease progression
|
|||||||||||||||||||||
Arm title
|
Arm B : Lanreotide + Non Steroidal Anti Androgens and LHRH-a | |||||||||||||||||||||
Arm description |
Lanreotide 120 mg injection every 28 days till progression or for a maximum of 24 months plus non steroidal anti androgens (e.g. bicalutamide 50 mg/day) and LHRH-a (e.g. triptorelin 3.75 mg/month) till progression. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Second line hormonal treatment + lanreotide 120 mg
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||
Dosage and administration details |
Lanreotide, non steroidal anti androgens and LHRH-a to be administered till progression or for a maximum of 24 months.
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A : Non-steroidal Anti Androgens + LHRH-a
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-steroidal anti androgens (e.g. bicalutamide 50 mg/day) plus Luteinizing Hormone-Releasing Hormone Analogues (LHRH-a) (e.g. triptorelin 3.75 mg/month) till progression. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B : Lanreotide + Non Steroidal Anti Androgens and LHRH-a
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lanreotide 120 mg injection every 28 days till progression or for a maximum of 24 months plus non steroidal anti androgens (e.g. bicalutamide 50 mg/day) and LHRH-a (e.g. triptorelin 3.75 mg/month) till progression. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Arm A : Non-steroidal Anti Androgens + LHRH-a
|
||
Reporting group description |
Non-steroidal anti androgens (e.g. bicalutamide 50 mg/day) plus Luteinizing Hormone-Releasing Hormone Analogues (LHRH-a) (e.g. triptorelin 3.75 mg/month) till progression. | ||
Reporting group title |
Arm B : Lanreotide + Non Steroidal Anti Androgens and LHRH-a
|
||
Reporting group description |
Lanreotide 120 mg injection every 28 days till progression or for a maximum of 24 months plus non steroidal anti androgens (e.g. bicalutamide 50 mg/day) and LHRH-a (e.g. triptorelin 3.75 mg/month) till progression. |
|
|||||||||||||
End point title |
Progression-free Survival [1] | ||||||||||||
End point description |
Study early terminated due to poor enrollment.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Week 96
|
||||||||||||
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 details provided. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Prostate Specific Antigen (PSA) Response | |||||||||
End point description |
Study early terminated due to poor enrollment.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 96
|
|||||||||
|
||||||||||
Notes [2] - Study early terminated due to poor enrollment [3] - Study early terminated due to poor enrollment |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Median Time to PSA Response | |||||||||
End point description |
Study early terminated due to poor enrollment.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 96
|
|||||||||
|
||||||||||
Notes [4] - Study early terminated due to poor enrollment [5] - Study early terminated due to poor enrollment |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Reduction in Chromogranin A Serum Levels | |||||||||
End point description |
Study early terminated due to poor enrollment
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline, Week 96
|
|||||||||
|
||||||||||
Notes [6] - Study early terminated due to poor enrollment [7] - Study early terminated due to poor enrollment |
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
AEs were reported from Baseline (visit 2) to visit 10 (Week 96 - End of study)
|
|||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All AEs documented for this study were treatment emergent. Overall, for 1 patient (100.0%) of Arm B at least one AE, at least one AE related to study treatment and at least one severe AE were reported.
|
|||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
|||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A : Non-steroidal Anti Androgens + LHRH-a
|
|||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||
Reporting group title |
Arm B : Lanreotide + Non-steroidal Antiandrogens and LHRH-a
|
|||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||
|
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
28 Oct 2011 |
- Inclusion of patients with stable metastatic disease and exclusion of the non metastatic patients (this required the change in study title)
- Inclusion of patients already treated with maximal androgen blockade (MAB) i.e. LHRHa + antiandrogen. This modified also the study design: to evaluate the efficacy in terms of PFS of the administration of second – line hormonal treatment (Arm A) versus second - line hormonal treatment + lanreotide (Arm B) (based on the definition of “second-line hormonal therapy” according to Italian guidelines - AIOM / Prostate Cancer 11-2009)
- The inclusion criterion relative to the serum creatinine was modified (new cutoff <1.5xULN)
- In order to avoid possible bias due to different type of treatment of patient at inclusion (MAB or LHRHa alone), a new randomization list has been generated to account for stratification by type of treatment at inclusion
- Inclusion of patients with stable metastatic disease besides the non metastatic patients already required in the main protocol (this required the change in study title)
- Exclusion of patients with visceral metastasis and patients taking narcotic for analgesia for bone pain. This was introduced to avoid the enrolment of patients with an high stage disease which could require anticancer therapy |
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
Study terminated due to poor enrollment |