Back to results

Vinorelbine in Mesothelioma (VIM)

Primary Purpose

Mesothelioma

Status

Completed

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Vinorelbine

Active Symptom Control

About this trial

This is an interventional treatment trial for Mesothelioma focused on measuring Mesothelioma, Vinorelbine, BRCA1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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.

Exclusion Criteria:

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
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

Sites / Locations

Wales Cancer Trials Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Active Symptom Control

Vinorelbine

Arm Description

Active symptom control includes palliative care and standard care methods used to manage symptoms

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).

Outcomes

Primary Outcome Measures

Overall Survival

Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.

Secondary Outcome Measures

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

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.

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.

Full Information

NCT ID

NCT02139904

First Posted

May 9, 2014

Last Updated

October 4, 2021

Sponsor

Wales Cancer Trials Unit

Collaborators

Pierre Fabre Laboratories

1. Study Identification

Unique Protocol Identification Number

NCT02139904

Brief Title

Vinorelbine in Mesothelioma

Acronym

VIM

Official Title

A Randomised Phase II Trial of Oral Vinorelbine as Second Line Therapy for Patients With Malignant Pleural Mesothelioma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

March 1, 2016 (Actual)

Primary Completion Date

March 17, 2021 (Actual)

Study Completion Date

March 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wales Cancer Trials Unit

Collaborators

Pierre Fabre Laboratories

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mesothelioma

Keywords

Mesothelioma, Vinorelbine, BRCA1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

154 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active Symptom Control

Arm Type

Placebo Comparator

Arm Description

Active symptom control includes palliative care and standard care methods used to manage symptoms

Arm Title

Vinorelbine

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Vinorelbine

Other Intervention Name(s)

Navelbine

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Active Symptom Control

Primary Outcome Measure Information:

Title

Overall Survival

Description

Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

2 years

Title

Number of serious adverse events reported

Description

Time Frame

2 years

Title

BRCA1 status in blood and tumour samples

Description

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.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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. Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dean Fennell, Professor

Organizational Affiliation

University of Leicester

Official's Role

Study Chair

Facility Information:

Facility Name

Wales Cancer Trials Unit

City

Cardiff

ZIP/Postal Code

CF14 4YS

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35706488

Citation

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.

Results Reference

derived

Links:

URL

https://www.cardiff.ac.uk/centre-for-trials-research

Description

Related trial information

Learn more about this trial

Vinorelbine in Mesothelioma

We'll reach out to this number within 24 hrs