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

Our plain-English summary of 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, by N.L. de Boer, J.P. van Kooten, J.W.A. Burger, et al (BMJ Open, 2019).

The study

• Authors: N.L. de Boer, J.P. van Kooten, J.W.A. Burger, C. Verhoef, J.G.J.V. Aerts, E.V.E. Madsen
• Journal: BMJ Open
• Published: 2019;9(5):e026779
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

Methods And Analysis: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.

Intervention: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

Ethics And Dissemination: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

Trial Registration Number: NTR7060. EudraCT: 2017-000897-12; Pre-Results.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article is a trial protocol. It described the plan for the MESOPEC trial and reported no results. MESOPEC is an open-label, single-arm, single-centre phase II trial at Erasmus MC in Rotterdam, the Netherlands, for adults with epithelioid malignant peritoneal mesothelioma, a cancer of the lining of the abdomen. All patients receive standard cytoreductive surgery with heated chemotherapy delivered into the abdomen (CRS-HIPEC). Four to six weeks before surgery, white blood cells are collected and grown into dendritic cells. These are loaded with material from five mesothelioma cell lines to make the vaccine, called MesoPher. Three vaccinations are given every two weeks, starting 8 to 10 weeks after surgery, with boosters 3 and 6 months after the first vaccination. The main aim is feasibility, defined as 15 of 20 patients (75%) completing the whole process. Secondary aims are safety and immune response. The authors stated that the trial is small and cannot measure tumour response on scans. If the treatment is safe and feasible, they consider a phase III trial on survival warranted. The trial did not study asbestos exposure.

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: Protocol (study plan) for an open-label, single-arm, single-centre phase II clinical trial; no results reported
• Who was studied: Adults with histologically or cytologically confirmed epithelioid malignant peritoneal mesothelioma, treated at Erasmus MC, Rotterdam, the Netherlands. The target sample size is 20 patients and first enrolment was March 2018.
• Exposure: The intervention under study is dendritic cell based immunotherapy (MesoPher: the patient's own dendritic cells loaded with allogeneic mesothelioma tumour lysate, PheraLys). It is given three times every two weeks starting 8 to 10 weeks after CRS-HIPEC, plus boosters 3 and 6 months after the first vaccination. Asbestos exposure is mentioned only as background and was not studied.
• The authors' conclusion: As a protocol, the article draws no conclusions from data. The authors stated that if dendritic cell therapy is found safe and feasible after CRS-HIPEC, a phase III study is warranted to determine its effect on survival.
• Limitations the authors state:
  • The small number of patients, owing to the rarity of the disease
  • Radiological response to the treatment cannot be determined, because after surgery the disease is not detectable on scans
  • The effect on overall survival can only be determined after longer follow-up

Topics

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

Medical terms in this study, explained in our Lexicon: Immunotherapy, Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Clinical Trial, Neoplasm, Asbestos Exposure, Palliative Care.

Related studies

• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Radiological predictors of complete cytoreduction in 59 patients with peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a UK referral centre — A. Chandramohan, A. Thrower, et al. (2017)
• A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for standardizing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma — T.P. Batista, B.J.Q. Sarmento, et al. (2017)
• Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy (HIPEC) by Minimally Invasive Approach, an Initial Experience — A. Arjona-Sanchez, S. Rufian-Peña, et al. (2018)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)

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