Intraperitoneal paclitaxel for patients with primary malignant peritoneal mesothelioma: a phase I/II dose escalation and safety study-INTERACT MESO

Our plain-English summary of Intraperitoneal paclitaxel for patients with primary malignant peritoneal mesothelioma: a phase I/II dose escalation and safety study-INTERACT MESO, by J.P. van Kooten, M.V. Dietz, N.A.D. Guchelaar, et al (BMJ Open, 2022).

The study

• Authors: J.P. van Kooten, M.V. Dietz, N.A.D. Guchelaar, A.R.M. Brandt-Kerkhof, S.L.W. Koolen, J.W.A. Burger, R.H.J. Mathijssen, C. Verhoef, J.G.J.V. Aerts, E.V.E. Madsen
• Journal: BMJ Open
• Published: 2022;12(6):e062907
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.

Methods And Analysis: The INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.

Ethics And Dissemination: The Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.

Trial Registration Number: NL9718. EudraCT: 2021-003637-11.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article was a study protocol, not a report of results. It described the planned INTERACT MESO trial at the Erasmus MC Cancer Institute in Rotterdam, the Netherlands. The trial was designed as a prospective, open-label, single-centre phase I study with a three-plus-three dose escalation design. It was for adults with primary malignant peritoneal mesothelioma, without disease outside the abdomen, who were not eligible for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A port would be placed under the skin with its catheter tip inside the abdominal cavity, and paclitaxel would be given through it weekly at planned flat doses of 100, 150 or 200 mg. The main aim was to find the maximum tolerable dose. Other aims were safety, toxicity, feasibility, and how the drug behaves in the body. Recruitment started in February 2022, and one patient had been enrolled as of 17 May 2022. The article reported no treatment results and did not study asbestos exposure. The authors stated that further research would be needed to determine the effect on survival.

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 prospective, open-label, single-centre, phase I dose escalation trial (three-plus-three design); no results reported
• Who was studied: Planned: adult patients with primary malignant peritoneal mesothelioma, without extra-abdominal disease, not eligible for CRS-HIPEC, at Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Target sample size 11 to 21. Recruitment started February 2022, with one patient enrolled as of 17 May 2022.
• Exposure: Not an asbestos exposure study. The intervention was intraperitoneal paclitaxel monotherapy. It was to be given weekly through a peritoneal port-a-cath placed under the skin, with the catheter tip inside the peritoneal cavity. Planned dose levels were 100, 150 and 200 mg flat dose, initially for eight cycles. A dose de-escalation to 80 mg was planned if needed.
• The authors' conclusion: The authors stated that if the maximum tolerable dose is determined and the treatment is found to be safe, a larger phase III trial should be conducted to determine the effect on survival outcomes.
• Limitations the authors state:
  • The authors stated that as a phase I trial it is not designed to determine effectiveness; further research is needed to determine the effect on survival.
  • The authors stated that long-term follow-up is not applicable in this phase I trial.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Peritoneum, Cytoreductive Surgery, HIPEC, Palliative Care, Chemotherapy, Diagnostic Laparoscopy.

Related studies

• Unusually favorable outcome of 6 consecutive patients with diffuse malignant peritoneal mesothelioma treated with repeated doses of intraperitoneal paclitaxel. A case series — P.H. Sugarbaker, O.A. Stuart (2020)
• Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial — M.V. Dietz, K.L.A. Quintelier, et al. (2023)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study — N. van Zandwijk, N. Pavlakis, et al. (2017)
• Paclitaxel for malignant pleural mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group — J. van Meerbeeck, C. Debruyne, et al. (1996)
• Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer — L.L. Herscher, S.M. Hahn, et al. (1998)

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