Clinical Trial Results:
Phase III study of IV vinflunine in combination with methotrexate versus methotrexate alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based chemotherapy (study L00070 IN 309 F0)
Summary
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EudraCT number |
2011-005081-38 |
Trial protocol |
DE ES IT BE EE AT PL SK |
Global end of trial date |
23 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2019
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First version publication date |
06 Mar 2019
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Other versions |
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 309 F0
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02347332 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Pierre Fabre Médicament, Institut de Recherche Pierre Fabre
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Sponsor organisation address |
BP 13562, Toulouse, France, 31305
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Public contact |
Zahida Issiakhem, MD
Clinical Development Physician (Department Medical Unit) , Pierre Fabre Médicament,
Institut de Recherche Pierre Fabre
, +33 (0) 5 34 50 61 71, zahida.issiakhem@pierre-fabre.com
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Scientific contact |
Zahida Issiakhem, MD
Clinical Development Physician (Department Medical Unit) , Pierre Fabre Médicament,
Institut de Recherche Pierre Fabre
, +33 (0) 5 34 50 61 71, zahida.issiakhem@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 |
20 Oct 2017
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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 |
23 Nov 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the overall survival (OS) of intravenous (IV) vinflunine (VFL) in combination with methotrexate (MTX) versus MTX alone in incurable recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) patients who have failed platinum based chemotherapy.
Futility analysis showed that the probability of demonstrating a significant benefit in OS at the time of the final analysis was very low. Consequently, the sponsor decided to end trial and limit efficacy analysis to ITT patients. At the cut-off date October 20th 2017, 3 patients were ongoing and at the time of this report 1 patient is under compassional treatment. An addendum and update of the data on safety will be made once all patients are deceased and the global end of trial is reached.
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Protection of trial subjects |
The study was conducted according to Good Clinical Practices (GCPs) (CPMP/ICH/135/95), International Conference on Harmonisation (ICH) E11, the ethical principles that have their origins in the Declaration of Helsinki (1964) and its subsequent amendments. Each patient signed an Informed consent.
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Background therapy |
Vinflunine (VFL) is a microtubule inhibitor of the vinca-alkaloid class. Microtubules are an important chemotherapeutic target because of the crucial role they play during mitosis, particularly for rapidly dividing cancer cells. VFL inhibits tubulin assembly by perturbing microtubule dynamics and mitotic spindles without affecting assembled microtubules. An international program of phase II studies with VFL as a single agent has been carried out in chemonaïve patients, and also as salvage therapy in order to determine the tumour response in a large spectrum of solid tumours. In a phase III study, VFL given as second-line after failure of prior platinum-based chemotherapy demonstrated a survival advantage over best supportive care in advanced transitional cell carcinoma of the urothelial tract (TCCU). In a further phase III study, VFL showed similar efficacy to docetaxel in advanced non small cell lung cancer.Vinca-alkaloids have demonstrated activity in SCCHN; single agent vinorelbine showed activity after first-line cisplatin-based chemotherapy. VFL demonstrated superior antitumour activity to vinorelbine in preclinical animal models, and has well-established efficacy in the second-line treatment of TCCU and non small cell lung cancer after platinum failure. Vinca-alkaloids have been successfully combined with MTX in a variety of solid tumours including advanced TCCU, metastatic breast cancer and malignant mesothelioma. In patients with SCCHN who had relapsed after cisplatin plus 5 FU, a regimen combining vinorelbine, bleomycin and MTX showed activity with a response rate of 27% and acceptable toxicity. Recent preliminary phase I results of the vinflunine plus methotrexate combination in SCCHN, based on a clinical review, show encouraging antitumour activity and an acceptable safety profileTherefore the combination of VFL and MTX appears a promising salvage regimen after platinum failure. | ||
Evidence for comparator |
For patients with incurable recurrent/metastatic SCCHN who failed platinum-based therapy, single agent MTX at a dose of 40 mg/m2/week is considered as the best available evidence-based option. Also, other trials using this comparator have demonstrated that it is generally accepted as a reasonable choice, and is often used in general practice | ||
Actual start date of recruitment |
02 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 7
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Country: Number of subjects enrolled |
Belarus: 21
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
Brazil: 36
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Country: Number of subjects enrolled |
Estonia: 5
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Country: Number of subjects enrolled |
France: 68
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Country: Number of subjects enrolled |
Germany: 16
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Country: Number of subjects enrolled |
Italy: 38
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Country: Number of subjects enrolled |
Mexico: 5
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Country: Number of subjects enrolled |
Poland: 23
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Country: Number of subjects enrolled |
Russian Federation: 120
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Country: Number of subjects enrolled |
Slovakia: 5
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Country: Number of subjects enrolled |
Spain: 26
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Country: Number of subjects enrolled |
Taiwan: 28
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Country: Number of subjects enrolled |
Ukraine: 53
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Worldwide total number of subjects |
459
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EEA total number of subjects |
196
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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) |
357
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From 65 to 84 years |
102
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were stratified at inclusion by the following factors: performance status (0 versus 1), refractory or resistant to platinum versus other, prior radiotherapy, treatment with anti-epidermal growth factor receptor, centre, patients were randomly assigned in a 1:1 ratio to 1 of the 2 arms. | ||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Adult patients with histological or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx with a WHO performance status < 1 with adequate haematological, hepatic and renal function. Disease must have been documented as progressive during or after platinum based chemotherapy | ||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Screening
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients randomised to Arm A received: VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Vinflunine
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Investigational medicinal product code |
L0070
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Other name |
JAVLOR, (4’R) - 20’, 20’-difluoro 3'4’-dihydrovinorelbine L -(+) - tartrate (1 : 2)
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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 |
Patients randomised to arm A will receive vinflunine on day 1 as a 20 minute IV infusion at 280
mg/m² and methotrexate on days 1 and 8 as a bolus intravenous injection at 30 mg/m² of every
three-week cycle.
The total dose to be given will be calculated according to body surface area (BSA). In calculating
BSA, actual heights and weights should be used. BSA should be recalculated prior to the next cycle
dosing.
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Investigational medicinal product name |
Methotrexate
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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 bolus use
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Dosage and administration details |
On day 1, methotrexate will be administered by direct bolus injection through the side arm of the
remaining NS or 5% glucose solution bag after completion of vinflunine infusion.
On day 8, methotrexate will be administered though the side arm of a freely running NS or 5%
glucose solution IV infusion.
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Arm title
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Arm B | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through the side arm of a freely running NS or 5% glucose solution IV infusion. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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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 bolus use
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Dosage and administration details |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous
injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through
the side arm of a freely running NS or 5% glucose solution IV infusion.
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Period 2
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Period 2 title |
Overall Study
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients randomised to Arm A received: VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Vinflunine
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Investigational medicinal product code |
L0070
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Other name |
JAVLOR, (4’R) - 20’, 20’-difluoro 3'4’-dihydrovinorelbine L -(+) - tartrate (1 : 2)
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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 |
Patients randomised to arm A will receive vinflunine on day 1 as a 20 minute IV infusion at 280
mg/m² and methotrexate on days 1 and 8 as a bolus intravenous injection at 30 mg/m² of every
three-week cycle.
The total dose to be given will be calculated according to body surface area (BSA). In calculating
BSA, actual heights and weights should be used. BSA should be recalculated prior to the next cycle
dosing.
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Investigational medicinal product name |
Methotrexate
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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 bolus use
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Dosage and administration details |
On day 1, methotrexate will be administered by direct bolus injection through the side arm of the
remaining NS or 5% glucose solution bag after completion of vinflunine infusion.
On day 8, methotrexate will be administered though the side arm of a freely running NS or 5%
glucose solution IV infusion.
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Arm title
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Arm B | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through the side arm of a freely running NS or 5% glucose solution IV infusion. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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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 bolus use
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Dosage and administration details |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous
injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through
the side arm of a freely running NS or 5% glucose solution IV infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Arm A
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Reporting group description |
Patients randomised to Arm A received: VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B
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Reporting group description |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through the side arm of a freely running NS or 5% glucose solution IV infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ARM A
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients randomised to Arm A received:
• VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and
• MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle.
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Subject analysis set title |
ARM B
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients randomised to Arm B, MTX was given at a dose of 40 mg/m²/week administered by direct bolus IV injection on Days 1, 8 and 15 of every three week cycle. One cycle of MTX is defined as a three week period.
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End points reporting groups
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Reporting group title |
Arm A
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Reporting group description |
Patients randomised to Arm A received: VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle. | ||
Reporting group title |
Arm B
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Reporting group description |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through the side arm of a freely running NS or 5% glucose solution IV infusion. | ||
Reporting group title |
Arm A
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Reporting group description |
Patients randomised to Arm A received: VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle. | ||
Reporting group title |
Arm B
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Reporting group description |
Patients randomised to arm B received methotrexate on a weekly basis as a bolus intravenous injection at the dose of 40 mg/m²/week. The drug was administered by direct injection through the side arm of a freely running NS or 5% glucose solution IV infusion. | ||
Subject analysis set title |
ARM A
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Patients randomised to Arm A received:
• VFL at a dose of 280 mg/m² on Day 1, over a 20 minute IV infusion, and
• MTX administered at a dose of 30 mg/m² by direct bolus IV injection on Days 1 and 8 of every three week cycle.
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Subject analysis set title |
ARM B
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Patients randomised to Arm B, MTX was given at a dose of 40 mg/m²/week administered by direct bolus IV injection on Days 1, 8 and 15 of every three week cycle. One cycle of MTX is defined as a three week period.
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End point title |
Overall survival (OS) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30 months
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Attachments |
Overall Survival (ITT) in months Overall Survival (ITT) in months Fig |
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Statistical analysis title |
Overall Survival (months) ITT | ||||||||||||
Comparison groups |
Arm A v Arm B
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Progression free Survival (ITT) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Progression Free Survival (ITT) in months) Progression Free Survival (ITT) in months - Fig |
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Statistical analysis title |
Progression Free Survival (months) (ITT) | ||||||||||||
Comparison groups |
Arm A v Arm B
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
- |
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End point title |
Objective Response Rate (ITT) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Objective Response Rate (ORR) [ITT] |
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Statistical analysis title |
Objective Response Rate | ||||||||||||
Statistical analysis description |
The best response designation recorded from the date of randomisation until disease progression.
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Comparison groups |
Arm A v Arm B
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
- |
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End point title |
Disease Control Rate (DCR) (ITT) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Disease Control Rate (DCR) [ITT] |
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No statistical analyses for this end point |
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End point title |
Duration Of Response (ITT) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Duration of Response (Months) [ITT] Duration of Response (months) [ITT] |
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No statistical analyses for this end point |
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End point title |
Duration of Disease Control | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Duration of Disease Control (months) [ITT] Duration of Disease Control (months) [ITT] Fig |
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No statistical analyses for this end point |
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End point title |
Time to Treatment Failure | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 months
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Attachments |
Time to Treatment Failure (months) [ITT] Time to Treatment Failure (months) [ITT] |
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No statistical analyses for this end point |
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End point title |
Time to First response [ITT] | ||||||||||||
End point description |
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End point type |
Secondary
|
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End point timeframe |
30 months
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Attachments |
Time to Time to First Response (months) [ITT] Time to First Response (months) [ITT] |
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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 |
4 years 6 months 29 days.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
VFL + MTX
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MTX.
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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04 Feb 2014 |
PA01
Three new exclusion criteria were added:
• albumin level < 35 g/L,
• weight loss ≥ 5% within the last 3 months,
• recurrent pulmonary or upper airways infections (3 times or more in the last 3 months) requiring antibiotics and/or any infection requiring antibiotics within the last month before study entry.
• Permitted the eligibility of patients who present with synchronous squamous cell carcinomas of head and neck region.
• Included data from a dose-finding and pharmacokinetic phase I study (L00070 IN 117 F0) evaluating the combination of VFL with MTX.
• Implemented changes in the treatment modifications guidelines.
• Implemented changes on SAE reporting.
• Shortened the inclusion period from 24 months to 19 months.
• Increased the number of participating sites. |
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19 Mar 2014 |
PA04:
Based on requests from the French Ethics Committee issued on 14 March 2014 that led to protocol version #4, the following modifications were implemented:
• The exclusion criterion ‘known hypersensitivity to vinca-alkaloids or MTX’ was deleted as patients with prior treatment with vinca-alkaloids and MTX were excluded.
• Mentioned that creatinine clearance is calculated by the Cockroft-Gault formula.
• Specified that VFL metabolism depends on the isoform CYP3A4.
• Stated that clinical data of VFL-related neurotoxicity are moderate, frequent but reversible.
• Added mouthwashes as prophylaxis of oral mucositis.
• Updated the references. |
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21 Mar 2014 |
PA05:
Based on further requests from ANSM issued on 21 March 2014 leading to protocol version #5 the following modifications were implemented:
• Deleted text stating that ECGs were performed in the first 40 patients who were to be analysed in the early safety analysis treated patients.
• Specified the measures that were to be taken in case of QT/QTc interval > 500 msec (Grade 3). |
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10 Apr 2014 |
PA03:
Based on the comments and requests from the French Competent Authorities (ANSM) issued on 07 March 2014 that led to protocol version #3, the following modifications were implemented:
• Two new exclusion criteria were added:
• serum potassium < lower limit of normal,
• ECG demonstrating a QT/QTc interval > 480 msec.
• ECGs would be performed throughout the study treatment to further monitor patient’s safety.
• Men must use adequate methods of contraception throughout the study and for up to 3 months after the study treatment if their partners were women of childbearing potential.
• The exclusion criterion ‘known hypersensitivity to vinca-alkaloids or MTX’ was deleted as patients with prior treatment with vinca-alkaloids and MTX were excluded.
• Detailed the clinical symptoms/signs and radiological features of Posterior Reversible Encephalopathy Syndrome.
• Medications that prolong QT/QTc interval were to be avoided. A list of such medications was provided.
• Mentioned that creatinine clearance is calculated by the Cockroft-Gault formula.
• Specified that VFL metabolism depends on the isoform CYP3A4.
• Stated that clinical data of VFL-related neurotoxicity are moderate, frequent but reversible.
• Added mouthwashes as prophylaxis of oral mucositis.
|
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23 Nov 2015 |
PA10: (submitted only in Belgium, France, Spain, Poland, Estonia, Russia, Belarus and Ukraine)
• The results of the second interim analysis (August 2015) of efficacy of Study L00070 IN 309 F0 led the IDMC to recommend the implementation of a futility analysis of overall survival which is the primary endpoint of Study L00070 IN 309 F0.
• The results of the futility analysis showed that the probability of demonstrating a significant benefit in overall survival at the time of the final analysis was very low.
• As a consequence, the sponsor stopped the recruitment of study patients on 16 October 2015.
• This amendment:
• updated the protocol to reflect the sponsor’s decision to stop study recruitment,
• deleted ‘adequate renal function serum creatinine ≤ ULN’ in the inclusion criterion #11 in order to fulfil the SmPC of VFL. |
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05 Feb 2016 |
PA11
• Clarified amendment PA10 with regards to the participation of the patient after the end of treatment phase.
• Modified the statistical analysis according to the PA10 amendment. |
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Interruptions (globally) |
|||
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. | |||
Abbreviated CSR. Futility analysis showed that the probability of demonstrating a significant benefit in OS at the time of the final analysis was very low. Consequently, the sponsor decided to end trial and limit efficacy analysis to ITT patients. |