MesotheliomaPhase 2VIMNCT02139904
Vinorelbine in Mesothelioma
A Phase 2 study testing Vinorelbine in people with Mesothelioma, run by Wales Cancer Trials Unit at 1 site in United Kingdom.
Trial summary
This study is for patients with malignant mesothelioma of the lung lining (called pleura) who have had previous chemotherapy with a platinum-based regimen whose disease has progressed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma
- What is being tested?
- Vinorelbine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 154 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2016to 17 Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed histological diagnosis of malignant pleural mesothelioma. The same block or 10 unstained slides should be available for translational research
- Prior treatment with first-line standard platinum doublet based chemotherapy only
- Evidence of disease progression according to CT scan
- Life expectancy ≥ 3 months
- ECOG performance status 0-2
- Men or women aged 18 years or over
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- Willing to consent to provide blood and tissue for translational research
- Measurable lesions by modified RECIST
- Adequate organ function, including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, WBC >3 x 109/L, haemoglobin ≥ 100g/L, platelets ≥ 100 x 109/L; adequate liver function: Bilirubin <1.5 x ULN AST/ALT 1.5- 2.5 x ULN.
- Patients with reproductive potential (male or female), who are sexually active during the duration of the trial or the drug washout period, should be prepared to use two effective forms of contraception throughout their participation in the trial and for at least three months after the last dose of vinorelbine.
- Patients must provide informed consent prior to any study specific procedures.
Who cannot join
- Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission or patients with a diagnosis of basal cell carcinoma of the skin.
- Have received treatment with an agent that has not received regulatory approval, within 30 days of study entry.
- Are pregnant or breastfeeding.
- Uncontrolled CNS disease.
- Known contraindication or hypersensitivity to vinorelbine or other vinca alkaloids or to any of the constituents
- Any disease significantly affecting absorption
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- Previous significant surgical resection of stomach or small bowel
- Yellow fever vaccine within 30 days of consent
- Previous vinca alkaloid chemotherapy
- Palliative radiotherapy within the RECIST area in the 4 weeks prior to baseline CT chest up until randomisation.
- Patients that are unable to swallow
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Phase II Trial of Oral Vinorelbine as Second Line Therapy for Patients With Malignant Pleural Mesothelioma
This study is for patients with malignant mesothelioma of the lung lining (called pleura) who have had previous chemotherapy with a platinum-based regimen whose disease has progressed. Malignant pleural mesothelioma (MPM) is an aggressive, frequently drug resistant, and incurable disease that is increasing in incidence in the UK and worldwide. All patients with MPM will relapse following first line chemotherapy and at present, there is no standard treatment available for patients in the second line setting. The vinca alkaloid chemotherapy drug vinorelbine has shown promising activity in a single arm UK trial. However to date, there has been no randomised evaluation of vinorelbine in mesothelioma in the second line setting. In addition, there have been no trials which have looked at underlying molecular changes in mesothelioma which may predict vinorelbine efficacy; This might allow vinorelbine to be used in patients only where there is a chance of benefit. Studies suggest that vinorelbine requires a gene called BRCA1 (shown to be absent in 38% of mesothelioma cases) in order to induce cell death in mesothelioma. The VIM trial aims to establish whether vinorelbine in patients with MPM helps them live longer and whether the BRCA1 gene is helpful in selecting patients most likely to benefit from treatment.
Patients will be randomised (1:2) to receive either active symptom control (ASC) (which is all supportive care deemed necessary for pain management excluding disease modifying treatment) or ASC with vinorelbine. Patients will continue vinorelbine treatment until evidence of disease progression (or unacceptable toxicity to the drug or patient withdrawal). If vinorelbine activity is demonstrated, we will use the results from this trial to inform the design of a future phase III trial.
- Conditions
- Mesothelioma
- Being tested
- Vinorelbine, Active Symptom Control
- Keywords
- Mesothelioma, Vinorelbine, BRCA1
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinorelbineDrug
Also called Navelbine
Vinorelbine was first licensed in the UK for Non-Small Cell Lung Cancer (NSCLC) and advanced breast cancer in 1997. Vinorelbine (Navelbine®) is a semi-synthetic, third generation, vinca alkaloid. The cytotoxic effect of vinorelbine is through the disruption of mitotic spindle formation, blocking mitosis at the G2-M stage resulting in cell death.
Active Symptom ControlOther
| Study group | Role | What they receive |
|---|---|---|
| Active Symptom Control | Placebo comparator | Active symptom control includes palliative care and standard care methods used to manage symptoms Receives: Other: Active Symptom Control |
| Vinorelbine | Active comparator | Active symptom control (ASC) as per local practice plus vinorelbine administered at a dose of 60mg/m2 orally on day 1, day 8 and day 15 on a 3- weekly cycle, incrementing to 80mg/m2 weekly on a 3-weekly cycle in the absence of any significant toxicity for subsequent cycles. Patients will continue chemotherapy until evidence of radiological progression (or unacceptable toxicity or patient withdrawal). Receives: Drug: Vinorelbine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.
Measured: 2 years
Secondary outcomes (3)
Progression Free Survival
Anti-tumour activity of vinorelbine will also be measured by progression free survival. We will document time from randomisation to any disease progression and/or death, defined according to strict RECIST v1.1. Lesions will be compared with baseline measurements to assess progression
Measured: 2 years
Number of serious adverse events reported
The toxicity profile of oral vinorelbine in this setting will be used to assess safety. An independent data monitoring committee will convene and assess safety 6 months after the first patient has been randomised. If the trial is deemed safe to continue then safety will be assessed again approx every 6 months. Toxicity data will be assessed alongside serious adverse events.
Measured: 2 years
BRCA1 status in blood and tumour samples
Tumour and blood samples will be collected for future translational research. BRCA1 expression as a putative predictor of vinorelbine sensitivity will be measured primarily in the samples.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study start1 Mar 2016
- Primary completion17 Mar 2021
- Study completion17 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MesotheliomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wales Cancer Trials Unit
- Sponsor type
- University, hospital or other
- Collaborators
- Pierre Fabre Laboratories
- Responsible party
- Sponsor
- Investigators
- Dean Fennell, Professor, Study chair, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139904
- Sponsor's protocol ID
- UNOLE 0329
- Acronym
- VIM
- Status last verified
- Oct 2021
- First submitted
- 9 May 2014
- Last updated
- 12 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fennell DA, Porter C, Lester J, Danson S, Taylor P, Sheaff M, Rudd RM, Gaba A, Busacca S, Nixon L, Gardner G, Darlison L, Poile C, Richards C, Jordan PW, Griffiths G, Casbard A. Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial. EClinicalMedicine. 2022 May 19;48:101432. doi: 10.1016/j.eclinm.2022.101432. eCollection 2022 Jun.
PubMed 35706488
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Trial of Oral Vinorelbine as Second Line Therapy for Patients With Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT02139904
- Acronym / sponsor ID
- VIM / UNOLE 0329
- Conditions
- Mesothelioma
- Keywords
- Mesothelioma, Vinorelbine, BRCA1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- Wales Cancer Trials UnitUniversity, hospital or other
- Collaborators
- Pierre Fabre Laboratories
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 17 Mar 2021 (actual)
- Study completion
- 17 Mar 2021 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with malignant mesothelioma of the lung lining (called pleura) who have had previous chemotherapy with a platinum-based regimen whose disease has progressed. Malignant pleural mesothelioma (MPM) is an aggressive, frequently drug resistant, and incurable disease that is increasing in incidence in the UK and worldwide. All patients with MPM will relapse following first line chemotherapy and at present, there is no standard treatment available for patients in the second line setting. The vinca alkaloid chemotherapy drug vinorelbine has shown promising activity in a single arm UK trial. However to date, there has been no randomised evaluation of vinorelbine in mesothelioma in the second line setting. In addition, there have been no trials which have looked at underlying molecular changes in mesothelioma which may predict vinorelbine efficacy; This might allow vinorelbine to be used in patients only where there is a chance of benefit. Studies suggest that vinorelbine requires a gene called BRCA1 (shown to be absent in 38% of mesothelioma cases) in order to induce cell death in mesothelioma. The VIM trial aims to establish whether vinorelbine in patients with MPM helps them live longer and whether the BRCA1 gene is helpful in selecting patients most likely to benefit from treatment.
Patients will be randomised (1:2) to receive either active symptom control (ASC) (which is all supportive care deemed necessary for pain management excluding disease modifying treatment) or ASC with vinorelbine. Patients will continue vinorelbine treatment until evidence of disease progression (or unacceptable toxicity to the drug or patient withdrawal). If vinorelbine activity is demonstrated, we will use the results from this trial to inform the design of a future phase III trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Symptom Control | Placebo comparator | Other: Active Symptom ControlActive symptom control includes palliative care and standard care methods used to manage symptoms |
| Vinorelbine | Active comparator | Drug: VinorelbineActive symptom control (ASC) as per local practice plus vinorelbine administered at a dose of 60mg/m2 orally on day 1, day 8 and day 15 on a 3- weekly cycle, incrementing to 80mg/m2 weekly on a 3-weekly cycle in the absence of any significant toxicity for subsequent cycles. Patients will continue chemotherapy until evidence of radiological progression (or unacceptable toxicity or patient withdrawal). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Confirmed histological diagnosis of malignant pleural mesothelioma. The same block or 10 unstained slides should be available for translational research
- Prior treatment with first-line standard platinum doublet based chemotherapy only
- Evidence of disease progression according to CT scan
- Life expectancy ≥ 3 months
- ECOG performance status 0-2
Key exclusion criteria (11 listed)
- Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission or patients with a diagnosis of basal cell carcinoma of the skin.
- Have received treatment with an agent that has not received regulatory approval, within 30 days of study entry.
- Are pregnant or breastfeeding.
- Uncontrolled CNS disease.
- Known contraindication or hypersensitivity to vinorelbine or other vinca alkaloids or to any of the constituents
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 |
|---|---|---|
| VinorelbineAlso: NavelbineVinorelbine was first licensed in the UK for Non-Small Cell Lung Cancer (NSCLC) and advanced breast cancer in 1997. Vinorelbine (Navelbine®) is a semi-synthetic, third generation, vinca alkaloid. The cytotoxic effect of vinorelbine is through the disruption of mitotic spindle formation, blocking mitosis at the G2-M stage resulting in cell death. | Drug | Vinorelbine |
| Active Symptom Control | Other | Active Symptom Control |
Primary outcome
Overall Survival
Time frame: 2 years
Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.
3 secondary outcomes
Progression Free Survival
Time frame: 2 years
Number of serious adverse events reported
Time frame: 2 years
BRCA1 status in blood and tumour samples
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Derived from this study: PubMed 35706488Fennell DA, Porter C, Lester J, Danson S, Taylor P, Sheaff M, Rudd RM, Gaba A, Busacca S, Nixon L, Gardner G, Darlison L, Poile C, Richards C, Jordan PW, Griffiths G, Casbard A. Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial. EClinicalMedicine. 2022 May 19;48:101432. doi: 10.1016/j.eclinm.2022.101432. eCollection 2022 Jun.
- Related trial informationLink provided by the sponsor.
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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.
Dean Fennell, Professor study chair
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vinorelbine in people with Mesothelioma, run by Wales Cancer Trials Unit at 1 site in United Kingdom.
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 11 inclusion and 11 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 12 Oct 2021. 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 United Kingdom. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02139904, which also lists 1 linked publication.
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 12 Oct 2021.