Recurrent or Metastatic Head and Neck CarcinomaPhase 3NCT02347332
Phase III Study of Vinflunine Plus Methotrexate Versus Methotrexate Alone in Patients With Head and Neck Cancer
A Phase 3 study testing Vinflunine and Methotrexate in people with Recurrent or Metastatic Head and Neck Carcinoma, run by Pierre Fabre Medicament at 1 site in France.
Trial summary
For patients relapsing after platinum-based therapy, few data are available. The current use of cetuximab associated with radiotherapy in localized disease and associated with platinum-based chemotherapy in the first-line setting stresses the need for new therapeutic options at later stages of SCCHN.Vinca-alkaloids… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Recurrent or Metastatic Head and Neck Carcinoma
- What is being tested?
- Vinflunine and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 459 participants
- Where
- 1 siteFrance
- Study dates
- 25 Apr 2014to 23 Nov 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma
- Documented progressive disease after chemotherapy for locoregionally advanced or recurrent/metastatic SCCHN which included a platinum derivative
- Measurable or non measurable disease
- adequate haematological, hepatic and renal functions
- WHO performance status < 1
Who cannot join
- Nasopharyngeal carcinoma
- History of brain or leptomeningeal involvement
- Albumin level < 35 g/L
- Patients with weight loss ≥ 5% within the last 3 months
- Grade > 2 peripheral neuropathy at study entry
- "Third space" fluids (pleural effusion, ascites, massive edema)
- Prior treatment with vinca-alkaloids and methotrexate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
For patients relapsing after platinum-based therapy, few data are available. The current use of cetuximab associated with radiotherapy in localized disease and associated with platinum-based chemotherapy in the first-line setting stresses the need for new therapeutic options at later stages of SCCHN.Vinca-alkaloids demonstrated activity in SCCHN. Vinflunine demonstrated superior antitumour activity to vinorelbine in preclinical animal models. 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 profile. Therefore the combination of vinflunine and methotrexate appears a promising salvage regimen after platinum failure.
The present study has been designed as a multicenter, randomised phase III study which will compare the combination of IV vinflunine with methotrexate to methotrexate alone in SCCHN patients having failed platinum-based therapy.
Read the detailed description
This study was designed to compare the OS of VFL plus MTX versus MTX alone in patients with SCCHN who had failed platinum-based chemotherapy.
The trial was designed in accordance with current standards used routinely in oncology phase III trials and used established methods of assessment. The RECIST (version 1.1) and NCI CTCAE (version 3.0) guidelines are internationally recognised methods for assessing efficacy and tolerance, respectively.
The patient population was appropriate for this type of phase III study and included adult patients with recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, who had received prior chemotherapy regimens with documented progression. This population of patients was considered appropriate to meet the study objectives.
Recent preliminary phase I results of the VFL plus MTX combination in SCCHN, reported in a clinical review, showed encouraging antitumour activity and an acceptable safety profile A number of chemotherapy agents have been reported as having single-agent activity in SCCHN. However, reliable evidence of efficacy in the second-line setting is lacking, and there is currently no established standard of care. MTX used alone as the reference regimen at a dose of 40 mg/m2/week can be 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.
The efficacy and safety assessments employed in this study are standard measures routinely used in studies of this type
- Being tested
- Vinflunine, Methotrexate
- Keywords
- Vinflunin, Vinflunin + Methotrexate, Metastatic Squamous Cell Carcinoma of the Head and Neck
- Medical subject headings
- Recurrence, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinflunineDrug
Also called JAVLOR, VFL
MethotrexateDrug
Also called MTX
| Study group | Role | What they receive |
|---|---|---|
| Vinflunine plus methotrexate | Experimental | vinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks Receives: Drug: Vinflunine |
| Methotrexate | Active comparator | methotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival in the ITT Population (Months)
Time from randomization to the date of death or last follow-up. The survival duration of patients still alive, was censored at the date of last contact or last follow-up.
Measured: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
Secondary outcomes (4)
Progression Free Survival
Time measured from the date of randomisation until date of progression or death from any cause (whichever came first)
Measured: an expected average of 4 months
Objective Response Rate (ORR)
The objective response is defined as the best response designation recorded across all time points from the date of randomisation until disease progression.
Measured: 6 weeks
Disease Control Rate
Percentage of best overall responses CR, PR and SD in the analysed population
Measured: 30 months
Duration of Response
Duration of objective response will be measured for responders (CR+PR) from the time for CR or PR until the 1st date of documentation of recurrent or progressive disease or the date of death any cause.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2015 (estimated)
- Study start25 Apr 2014
- Primary completion20 Oct 2017
- Study completion23 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent or Metastatic Head and Neck CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 459 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pierre Fabre Medicament
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zahida Issiakhem, MD, Study director, Institut de Recherche Pierre Fabre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02347332
- Sponsor's protocol ID
- L00070 IN 309 F0
- Status last verified
- Feb 2019
- First submitted
- 18 Nov 2014
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02347332
- Acronym / sponsor ID
- L00070 IN 309 F0
- Keywords
- Vinflunin, Vinflunin + Methotrexate, Metastatic Squamous Cell Carcinoma of the Head and Neck
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 459 participants (actual)
- Lead sponsor
- Pierre Fabre MedicamentIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2014 (actual)
- Primary completion
- 20 Oct 2017 (actual)
- Study completion
- 23 Nov 2018 (actual)
- First posted
- 27 Jan 2015 (estimated)
- Results
- Posted 4 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For patients relapsing after platinum-based therapy, few data are available. The current use of cetuximab associated with radiotherapy in localized disease and associated with platinum-based chemotherapy in the first-line setting stresses the need for new therapeutic options at later stages of SCCHN.Vinca-alkaloids demonstrated activity in SCCHN. Vinflunine demonstrated superior antitumour activity to vinorelbine in preclinical animal models. 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 profile. Therefore the combination of vinflunine and methotrexate appears a promising salvage regimen after platinum failure.
The present study has been designed as a multicenter, randomised phase III study which will compare the combination of IV vinflunine with methotrexate to methotrexate alone in SCCHN patients having failed platinum-based therapy.
Detailed description
This study was designed to compare the OS of VFL plus MTX versus MTX alone in patients with SCCHN who had failed platinum-based chemotherapy.
The trial was designed in accordance with current standards used routinely in oncology phase III trials and used established methods of assessment. The RECIST (version 1.1) and NCI CTCAE (version 3.0) guidelines are internationally recognised methods for assessing efficacy and tolerance, respectively.
The patient population was appropriate for this type of phase III study and included adult patients with recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, who had received prior chemotherapy regimens with documented progression. This population of patients was considered appropriate to meet the study objectives.
Recent preliminary phase I results of the VFL plus MTX combination in SCCHN, reported in a clinical review, showed encouraging antitumour activity and an acceptable safety profile A number of chemotherapy agents have been reported as having single-agent activity in SCCHN. However, reliable evidence of efficacy in the second-line setting is lacking, and there is currently no established standard of care. MTX used alone as the reference regimen at a dose of 40 mg/m2/week can be 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.
The efficacy and safety assessments employed in this study are standard measures routinely used in studies of this type
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vinflunine plus methotrexate | Experimental | Drug: Vinfluninevinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks |
| Methotrexate | Active comparator | Drug: Methotrexatemethotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma
- Documented progressive disease after chemotherapy for locoregionally advanced or recurrent/metastatic SCCHN which included a platinum derivative
- Measurable or non measurable disease
- adequate haematological, hepatic and renal functions
- WHO performance status < 1
Key exclusion criteria (7 listed)
- Nasopharyngeal carcinoma
- History of brain or leptomeningeal involvement
- Albumin level < 35 g/L
- Patients with weight loss ≥ 5% within the last 3 months
- Grade > 2 peripheral neuropathy at study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VinflunineAlso: JAVLOR, VFL | Drug | Vinflunine plus methotrexate |
| MethotrexateAlso: MTX | Drug | Methotrexate |
Primary outcome
Overall Survival in the ITT Population (Months)
Time frame: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
Time from randomization to the date of death or last follow-up. The survival duration of patients still alive, was censored at the date of last contact or last follow-up.
4 secondary outcomes
Progression Free Survival
Time frame: an expected average of 4 months
Objective Response Rate (ORR)
Time frame: 6 weeks
Disease Control Rate
Time frame: 30 months
Duration of Response
Time frame: 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zahida Issiakhem, MD study director
Institut de Recherche Pierre Fabre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vinflunine and Methotrexate in people with Recurrent or Metastatic Head and Neck Carcinoma, run by Pierre Fabre Medicament at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival in the ITT Population (Months) (time frame: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.