Contact information
Type
Scientific
Primary contact
Dr Emma Keenan
ORCID ID
http://orcid.org/0000-0002-3884-1345
Contact details
Clinical Research Centre - Respiratory
Southmead Hospital
North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom
Type
Scientific
Additional contact
Dr Duneesha de Fonseka
ORCID ID
http://orcid.org/0000-0002-0060-9671
Contact details
Level 2
Learning and Research Building
Southmead Hospital
Bristol
BS10 5NB
United Kingdom
+44 117 4148041
Duneesha.defonseka@nbt.nhs.uk
Additional identifiers
EudraCT number
2015-004433-26
ClinicalTrials.gov number
Protocol/serial number
30497
Study information
Scientific title
A double-blind randomised controlled trial (RCT) to assess the feasibility of giving Zoledronic acid alongside chemotherapy in patients with mesothelioma to design a larger trial to assess the efficacy of Zoledronic acid alongside first line chemotherapy
Acronym
ZOL-A
Study hypothesis
The aim of this study is to investigate the feasibility of running a trial to establish the role of zoledronic acid (ZA) in patients who have mesothelioma and are undergoing or eligible for chemotherapy.
Ethics approval
East of England - Cambridge East Research Ethics Committee, 10/05/2016, ref: 16/EE/0105
Study design
Randomised; Interventional; Design type: Treatment, Drug, Imaging
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Respiratory disorders, Primary sub-specialty: Respiratory disorders; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs
Intervention
Patients will be randomised using varying block sizes on a 1:1 to one of two groups using web based software developed by Sealed Envelope. Randomisation will be stratified according to histological subtype. Participants will be allocated to either the IMP (Zoledronic acid) or placebo arms.
Participants in both arms of the trial will receive the infusion on the day of their chemotherapy, just prior to start of their chemotherapy treatment. They will have the same number of cycles of the IMP/placebo, as chemotherapy. Those who stop chemotherapy treatment early will stop IMP/placebo treatment too.
A renally adjusted dose of Zoledronic acid or placebo will be administered in 100ml of 0.9% saline via an intravenous cannula over 15 minutes alongside each session of chemotherapy (every 3 weeks, up to a maximum of 6 cycles). Randomised patients will be stratified by histological subtype and allocated to either Zoledronic acid or placebo. A third non-randomised arm of the trial is available to patients who decline chemotherapy but would like an opportunity to have Zoledronic acid on its own (every 3 weeks, up to a maximum of 6 cycles).
Follow up will occur after each cycle, at end of treatment and at 6 months, and involves information gathering on any AEs or SAEs relating to the IMP. Participants will also have blood tests at their follow-up appointments to ensure they are able to continue with the next cycle of chemotherapy treatment/IMP or placebo.
Intervention type
Other
Phase
Drug names
Primary outcome measure
1. Recruitment rate is recorded as the number of eligible participant who consent to participate in the study by 6 months
2. Acceptability of recruitment procedures, consent and randomisation, and data collection methods are measured through patient interviews conducted at 6 months
3. Tolerance of the IMP treatment will be measured by the proportion of patients who complete the full 6 cycles of treatment
4. Intolerance will be recorded for those who are unable to continue to with the IMP due to electrolyte disturbances or AEs relating to the IMP and come off treatment before completing 6 cycles
5. Efficacy data will be measured using CT scans, PET-CT scans and Mesothelin bloods tests. On CT a > 15% reduction in the modified RECIST score would be classed as a disease response. CT will be performed at post 3 cycles and at 6 months from enrolment
Secondary outcome measures
No secondary outcome measures
Overall trial start date
01/04/2016
Overall trial end date
31/05/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed diagnosis of MPM
2. WHO performance status 0-1
3. Eligible for first line chemotherapy treatment Measurable disease on CT as per modified RECIST criteria (tumour thickness > 5mm)
4. Ability to give informed consent
5. Aged 18 years and over
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 70; UK Sample Size: 70
Participant exclusion criteria
1. Not fit for chemotherapy due to performance status or other comorbidities Previous chemotherapy for MPM
2. IV bisphosphonates in the 3 months preceding randomisation
3. Significant renal disease (eGFR < 30ml/min in the last 4 weeks)
4. Hypocalcaemia (current hypocalcaemia on treatment, evidence of hypocalcaemia on most recent blood tests - should be within last 6 weeks)
5. Pregnancy or lactation Age
6. Age < 18 years
7. Known allergy to bisphosphonates or excipients of its preparation
8. Severe untreated dental caries
9. Concomitant participation in another drug trial for mesothelioma
Recruitment start date
01/09/2016
Recruitment end date
31/08/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Clinical Research Centre - Respiratory
Southmead Hospital
North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Results will be presented at an international mesothelioma research meeting such as International Mesothelioma interest Group (iMiG) and published in a peer reviewed scientific journal.
Intention to publish date
31/07/2018
Participant level data
Available on request
Basic results (scientific)
Publication list
2018 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/30157910