Zoledronic acid in the management of malignant pleural mesothelioma

ISRCTN	ISRCTN45536692
DOI	https://doi.org/10.1186/ISRCTN45536692
EudraCT/CTIS number	2015-004433-26
Secondary identifying numbers	30497

Submission date: 27/07/2016
Registration date: 09/08/2016
Last edited: 21/04/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-zoledronic-acid-and-chemotherapy-for-people-with-mesothelioma-zol-a

Contact information

Dr Emma Keenan
Scientific

Clinical Research Centre - Respiratory
Southmead Hospital
North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom

ORCID ID	0000-0002-3884-1345

Dr Duneesha de Fonseka
Scientific

Level 2, Learning and Research Building
Southmead Hospital
Bristol
BS10 5NB
United Kingdom

ORCID ID	0000-0002-0060-9671
Phone	+44 117 4148041
Email	Duneesha.defonseka@nbt.nhs.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment, Drug, Imaging
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	ZOL-A
Study objectives	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(s)	East of England - Cambridge East Research Ethics Committee, 10/05/2016, ref: 16/EE/0105
Health condition(s) or problem(s) studied	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
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 study start date	01/04/2016
Completion date	24/07/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 70; UK Sample Size: 70
Total final enrolment	22
Key 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
Key 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
Date of first enrolment	01/09/2016
Date of final enrolment	31/08/2017

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Clinical Research Centre - Respiratory

Southmead Hospital
North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom

Sponsor information

North Bristol NHS Trust
Hospital/treatment centre

Research & Innovation
Learning & Research Building
Southmead Hospital
Westbury-on-Trym
Bristol
BS10 5NB
England
United Kingdom

"ROR"	https://ror.org/036x6gt55

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	31/07/2018
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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.
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	29/08/2018		Yes	No
Basic results		22/07/2019	22/07/2019	No	No
Basic results			21/04/2020	No	No
HRA research summary			28/06/2023	No	No

Additional files

ISRCTN45536692_BasicResults_22Jul2019.pdf: uploaded 22/07/2019

Editorial Notes

21/04/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
22/07/2019: The basic results of this trial have been uploaded as an additional file.
03/07/2019: Internal review.
20/05/2019: The overall end date was changed from 31/05/2018 to 24/07/2018.
31/08/2018: Publication reference added.
06/06/2017: Cancer Help UK lay summary link added to plain English summary field