Zoledronic acid in the management of mesothelioma - a feasibility study (Zol-A Trial): study protocol for a randomised controlled trial

Our plain-English summary of Zoledronic acid in the management of mesothelioma - a feasibility study (Zol-A Trial): study protocol for a randomised controlled trial, by D. de Fonseka, A. Morley, L. Stadon, et al (Trials, 2018).

The study

• Authors: D. de Fonseka, A. Morley, L. Stadon, E. Keenan, S. Walker, S. Smith, J.E. Harvey, R.A. Cox, A. Dangoor, C. Comins, C. Rogers, A. Edey, A. Addeo, N.A. Maskell
• Journal: Trials
• Published: 2018;19(1):467
• Type of article: Randomized trial
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Nitrogen containing bisphosphonates such as zoledronic acid (ZA) are known to contain certain anti-cancer properties. These have been investigated in the past in various cancers such as breast, prostate and colon. ZA in particular has shown promising results in pre-clinical studies. We propose a multicentre double-blind randomised controlled feasibility study to assess the recruitment and acceptability of ZA/placebo alongside chemotherapy in malignant pleural mesothelioma (MPM).

Methods: Patients will be recruited for a 13-month period from October 2016 to November 2017. Eligible patients will be identified via the regional mesothelioma multidisciplinary team meeting. Those who receive chemotherapy will be randomised to receive either ZA or placebo alongside their chemotherapy. Those who decline chemotherapy will be offered to join the trial on the non-randomised open-labelled arm of the trial. Patients will receive a maximum of six cycles of ZA/placebo, at three-weekly cycles. All patients will be followed up for six months from randomisation. Semi-structured interviews to gather data on acceptability of trial procedures, tolerability of ZA and other relevant information will take place after the participants have completed their six cycles of treatment. For a better understanding about non-participation in mesothelioma trials we also aim to interview those who decline to take part in the trial.

Discussion: The qualitative and quantitative data gathered in this feasibility trial will hopefully pave the way to designing a robust full phase III trial to investigate the potential synergistic effect of ZA and current standard treatment for MPM, cisplatin-pemetrexed combination chemotherapy.

Trial Registration: ISRCTN Registry, ISRCTN45536692 . Registered on 9 August 2016. EudraCT no. 2015-004433-26.

In plain English

This article is a study protocol. It described a planned trial and reported no results. The authors set out a feasibility study, called the Zol-A trial, at three NHS sites in the South West region of the UK. Its purpose was to test whether patients with malignant pleural mesothelioma could be recruited to a trial of zoledronic acid, a bisphosphonate drug, given alongside standard cisplatin-pemetrexed chemotherapy. Patients receiving chemotherapy were to be randomly assigned to zoledronic acid or placebo, with neither patients nor investigators knowing which. Patients who were fit for chemotherapy but declined it could receive zoledronic acid alone, openly, in a separate non-randomised group. Treatment was planned for up to six cycles, three weeks apart, with the dose set by kidney function, and follow-up for six months. The main goal was to randomise 50 patients over 12 months. Interviews were planned to explore patients' experiences and their reasons for declining. Recruitment was planned from October 2016 to November 2017. The authors called the 50-patient target ambitious and hoped the data would help design a larger phase III trial.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for a planned multicentre, double-blind randomised controlled feasibility trial, with a non-randomised open-label arm and semi-structured interviews; no results reported
• Who was studied: Adults with a confirmed diagnosis of malignant pleural mesothelioma, WHO performance status 0 to 1, eligible for first-line chemotherapy, at three NHS sites in the South West region of the UK. The target was 50 randomised patients over a 12-month period, with recruitment from October 2016 to November 2017.
• Exposure: Treatment studied (not an asbestos exposure): intravenous zoledronic acid or placebo alongside cisplatin-pemetrexed chemotherapy, for up to six three-weekly cycles. The zoledronic acid dose depended on kidney function, from 4.0 mg (eGFR 60 mL/min or more) down to 3.0 mg (eGFR 30 to 39 mL/min), with none given below 30 mL/min. Patients who were fit for chemotherapy but declined it could receive zoledronic acid alone in an open-label arm.
• The authors' conclusion: The authors expressed the hope that the qualitative and quantitative data gathered in this feasibility trial would help in designing a full phase III trial of zoledronic acid with standard chemotherapy.
• Limitations the authors state:
  • The authors stated that the target of 50 randomised patients in 12 months across three sites is ambitious.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy, Pleural Mesothelioma, Multidisciplinary Team, Synergistic Effect, Cisplatin, Pemetrexed (Alimta).

Related studies

• CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial — D.A. Fennell, E. Kirkpatrick, et al. (2018)
• A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial — S. Gunatilake, F.J. Brims, et al. (2014)
• NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial — V. Gregorc, R.M. Gaafar, et al. (2018)
• Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial — C. Pinto, P.A. Zucali, et al. (2021)
• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)
• Multicenter randomized controlled trial of the management of unresectable malignant mesothelioma proposed by the British Thoracic Society and the British Medical Research Council — D.J. Girling, M.F. Muers, et al. (2002)

Browse more research in Trials, or return to medical research.