Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug 29;19(1):467.
doi: 10.1186/s13063-018-2851-9.

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

Duneesha de Fonseka  1 , Anna Morley  2 , Louise Stadon  2 , Emma Keenan  2 , Steven Walker  3 , Sarah Smith  4 , John E Harvey  3 , R Ashley Cox  5 , Adam Dangoor  6 , Charles Comins  6 , Christine Rogers  7 , Anthony Edey  8 , Alfredo Addeo  6 , Nick A Maskell  3
Affiliations

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

Duneesha de Fonseka et al. Trials. .

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.

Keywords: Malignant pleural mesothelioma; Mesothelin; Mesothelioma; PET-CT; Zoledronic acid.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study protocol and related documents were reviewed by East of England Cambridge East Research Ethics Committee (Ref 16/EE/0105). All participants will be asked for written consent before enrolling in the study. Participants will be given sufficient time to read the PIL and ask any questions relating to the study before consenting. Participants will also have the right to withdraw from the study at any time without having to give reason, if they change their mind regarding participation.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Trial flow chart
Fig. 2
Fig. 2
SPIRIT figure
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Milano MT, Zhang H. Malignant pleural mesothelioma: a population-based study of survival. J Thorac Oncol. 2010;5:1841–1848. doi: 10.1097/JTO.0b013e3181f1cf2b. - DOI - PubMed
    1. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–2644. doi: 10.1200/JCO.2003.11.136. - DOI - PubMed
    1. Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387:1405–1414. doi: 10.1016/S0140-6736(15)01238-6. - DOI - PubMed
    1. Rogers MJ. New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9:2643–2658. doi: 10.2174/1381612033453640. - DOI - PubMed
    1. Oades GM, Senaratne SG, Clarke IA, Kirby RS, Colston KW. Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate pathway, impairing Ras membrane localization in prostate cancer cells. J Urol. 2003;170:246–252. doi: 10.1097/01.ju.0000070685.34760.5f. - DOI - PubMed

Publication types

MeSH terms