Clinical Trial Results:
Phase II study assessing the maintenance treatment with vinflunine after first-line therapy with gemcitabine and cisplatin in patients with advanced or metastatic transitional cell carcinoma of the urothelial (TCCU) tract.
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Summary
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EudraCT number |
2011-000272-34 |
Trial protocol |
DE AT IT |
Global end of trial date |
14 Feb 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Dec 2018
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First version publication date |
16 Dec 2018
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Other versions |
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Summary report(s) |
Jasima final synopsis of CSR |
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 |
L00070-IN-214-P1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pierre Fabre medicament
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Sponsor organisation address |
45 place Abel Gance, Boulogne, France, 92100
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Public contact |
RIGGI, Pierre Fabre Medicament, +33 (0) 1.49.10.81.77, marcello.riggi@pierre-fabre.com
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Scientific contact |
RIGGI, Pierre Fabre Medicament, +33 (0) 1.49.10.81.77, marcello.riggi@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 |
13 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Feb 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Feb 2015
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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 is to evaluate the progression-free survival-rate (PFSrate) at 3 months of IV Vinflunine (VFL) as Maintenance Therapy (MT) for patients with advanced or metastatic Transitional cell carcinoma of the urothelium (TCCU) who achieved disease control (i.e. CR, PR or SD) after four cycles of first line standard doublet chemotherapy regimen with Gemcitabine-Cisplatin (GC).
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the current Declaration of Helsinki and was consistent with International Conference on Harmonization- Good Clinical Practice (ICH-GCP) and applicable regulatory requirements. The study was conducted in compliance with the protocol. The protocol, amendments, and the subject informed consent received Institutional Review Board (IRB)/Independent Ethics Committee IEC) approval/favourable opinion prior to initiation of the study and/or their implementation. Freely given written informed consent was to be obtained from every subject or his or her legally acceptable representative prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the trial.
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Background therapy |
Standard anti-emetic prophylaxis was recommended from the first cycle, prior to each treatment administration of vinflunine IV infusion and consisted of a single oral dose of dexamethasone 8 mg or equivalent dose of methylprednisolone. Laxatives and dietary measures were recommended, starting from day 1 of each vinflunine administration to day 5. For patients considered at increased risk of serious constipation, defined as history of chronic or refractory constipation, concomitant treatment with opioids, peritoneal carcinomatosis or abdominal tumour masses, persistent symptoms under vinflunine despite the days 1 to 5 dietary measures and laxatives administration, the use of a stool softener and a stimulant was recommended to maximise efficacy. | ||
Evidence for comparator |
The study was a non comparative, single arm, phase II trial as it aimed at evaluating the efficacy of single agent VFL as Maintenance Therapy following standard chemotherapy regimen by Gemcitabine-cisplatin (GC) combination regimen. Vinflunine is already approved as monotherapy in second line for patients with advanced/metastatic TCCU. | ||
Actual start date of recruitment |
30 Jun 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
28 Months | ||
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 |
Austria: 2
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Italy: 3
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Worldwide total number of subjects |
19
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EEA total number of subjects |
19
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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) |
9
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Between February 17th 2012 and July 24th 2013, a total of 20 patients with advanced or metastatic TCCU were registered at 11 investigational centres in Germany, Austria and Italy. 1 patient was withdrawn from study before first drug administration, he was considered as screen failure. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Treatment with GC chemotherapy was not part of this study. Inclusion into the trial had to take place only after completion of the 4 cycles of GC treatment. Only patients who achieved a complete response (CR), a Partial response (PR) or a stable disease (SD) after the 4 cycles of GC therapy were eligible to enter into the study to receive IV VFL. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Maintenance treatment (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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Vinflunine arm | ||||||||||||||||||||
Arm description |
The study population was patients aged ≥ 18 years with advanced or metastatic TCCU, who achieved disease control (CR, PR or SD) after four cycles of first line chemotherapy regimen with GC treatment. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Vinflunine
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Investigational medicinal product code |
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Other name |
Vinflunine ditartrate, Javlor
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Study drug administration had to start within 7 days after registration. Vinflunine was administered on Day 1, every 21 days as a 20 minute intravenous (IV) infusion.
For cycle 1, the starting dose of vinflunine was defined according to calculated creatinine clearance at registration (Cockroft-Gault formula), age, ECOG PS and prior pelvic irradiation. The treatment with vinflunine as MT was to be administered until documented disease progression, unacceptable toxicity, intercurrent illness or other reaction which could require discontinuation of study drug or patient refusal. As per the VFL Summary of Product Characteristics (SmPC), the recommended dose of VFL as single agent is 320 mg/m² as a 20 minute intravenous infusion every 3 weeks in patient without renal impairment (CrCl > 60 mL/mn) and 280 mg/m2 in patients with an ECOG PS of 1 or 0 with prior pelvic irradiation. In case of documented progression occurring before the first evaluation, the treatment was discontinued.
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Baseline characteristics reporting groups
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Reporting group title |
Vinflunine arm
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Reporting group description |
The study population was patients aged ≥ 18 years with advanced or metastatic TCCU, who achieved disease control (CR, PR or SD) after four cycles of first line chemotherapy regimen with GC treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Vinflunine arm
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Reporting group description |
The study population was patients aged ≥ 18 years with advanced or metastatic TCCU, who achieved disease control (CR, PR or SD) after four cycles of first line chemotherapy regimen with GC treatment. | ||
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End point title |
PFS Rate at 3 months [1] | ||||||
End point description |
As exploratory analysis, the primary efficacy endpoint was analysed on the first 20 patients included before termination of the study, that is to say, on the 19 patients, representing the ITT population and on the 15 evaluable patients for response.
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End point type |
Primary
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End point timeframe |
The primary efficacy parameter was the PFS rate at the fixed time point of 3 months after registration into the study. The PFS Rate has been estimated using Kaplan Meier Method.
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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: Due to early study termination, the analysis of the primary efficacy endpoint on the first 20 evaluable patients and on the total and required number of 70 evaluable patients for the second step Fleming design could not be performed. |
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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 |
Any AE occurring during the study period (starting after the first dose of medication and up to and including 30 days after the last dose of medication),spontaneously reported by the patient or observed by others was recorded.
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Adverse event reporting additional description |
Each patient was assessed for occurrence of adverse events throughout the study period. Adverse events were graded according to NCI- CTC AE criteria
The adverse events as well as baseline signs and symptoms were coded using the Medical Dictionary for Regulatory Activities (MedDRA).
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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 |
17.0
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Reporting groups
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Reporting group title |
Treated patients
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Reporting group description |
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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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30 Nov 2011 |
Study becoming an European study (Austria, Germany, Italy...) with updating number of centres involved. Including an update of the prohibited and non-recommended concomitant treatments regarding the use of dexamethasone as anti-emesis prophylaxis in the study. Including an update of Vinflunine IV Summary of product characteristics and Investigator's brochure. Including an update of registration form. |
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14 May 2012 |
Local requirement of performing monthly pregnancy test for women of childbearing potential during the treatment phase of patients included. |
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25 Jun 2012 |
Change of study selection criteria and the registration form (to involve patients > 75 years with dose adaptation, to other one additional week to complete the patients baseline clinical assessments, to adapt one exclusion criterion related to other malignancies + a cut-off value for haemoglobin. |
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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. | |||
| Due to difficulties in recruiting patients, the decision to stop the study before the first interim analysis was taken by the sponsor in agreement with the investigators. The study population consisted of 20 patients included, of whom 19 were treated | |||
