MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma

Our plain-English summary of MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma, by O. Sgarbura, S. Gourgou, D. Tosi, et al (Pleura and Peritoneum, 2019).

The study

• Authors: O. Sgarbura, S. Gourgou, D. Tosi, N. Bakrin, N. Bouazza, S. Delaine, H. De Forges, M. Pocard, F. Quénet
• Journal: Pleura and Peritoneum
• Published: 2019;4(2):20190010
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The standard frontline treatment of MPM is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) unless the peritoneal disease is considered unresectable. For unresectable patients the standard frontline treatment is a combination of cisplatin and pemetrexed but the prognosis remains ominous with only 13 months of overall survival (OS).

Methods: The proposed study is a multicenter randomized non-comparative study evaluating the association of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy vs. systemic chemotherapy alone as first-line treatment of MPM. Patients will be randomized with a 2:1 ratio using a minimization technique. Sixty-six patients have to be enrolled. Stratification will be performed according to histology (epithelioid vs. sarcomatoid and biphasic), presence of extraperitoneal disease and center. Primary objective is OS and secondary objectives include progression-free survival (PFS), safety, compliance, feasibility, conversion to resectability, histological response to treatment and quality of life.

Conclusions: We expect to show that intensification of the first line treatment with PIPAC for initially unresectable MPM patients increases OS.

Trial Registration: Prospective study. Clinicaltrials.gov: NCT03574493 EudraCT: 2019-001515-23.

In plain English

This article is a study protocol. It describes a planned trial, MESOTIP, and reports no patient results. The planned phase II multicenter randomized trial, at 10 French centers of the RENAPE network, was for previously untreated adults aged 18 to 75 with malignant peritoneal mesothelioma judged unresectable. Sixty-six patients were to be randomized 2:1, with 44 in an experimental arm and 22 in a control arm. The control arm was to receive 6 cycles of standard systemic chemotherapy with cisplatin and pemetrexed. The experimental arm was to receive the same 6 cycles plus 4 sessions of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC), one every 6 weeks. In PIPAC, cisplatin and doxorubicin are sprayed as an aerosol into the abdomen during laparoscopy. The main outcome was to be overall survival. Secondary outcomes included progression-free survival, safety and quality of life. The authors hypothesized that adding PIPAC would lead to better results. They noted that survival could be affected by unequal supportive care across regions, and that larger data on the PIPAC dose had not yet been published. The article does not discuss asbestos.

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 phase II multicenter randomized trial (2:1 randomization); no results reported
• Who was studied: Planned enrollment of 66 adults aged 18 to 75 with histologically confirmed, previously untreated malignant peritoneal mesothelioma not eligible for cytoreductive surgery, at 10 RENAPE network centers in France: 44 in the experimental arm and 22 in the control arm
• Exposure: Not an asbestos exposure study. The intervention studied was 4 PIPAC sessions (cisplatin 10.5 mg/m² plus doxorubicin 2.1 mg/m²) every 6 weeks, alternating with 6 cycles of systemic cisplatin 75 mg/m² plus pemetrexed 500 mg/m². This was compared with the 6 systemic cycles alone.
• The authors' conclusion: The authors hypothesized that adding PIPAC to standard systemic chemotherapy would lead to better results for patients in the experimental arm. This was a hypothesis, not a finding.
• Limitations the authors state:
  • Overall survival may be affected by confounding factors, such as unequal availability of supportive care across regions
  • The PIPAC cisplatin-doxorubicin dose came from a phase I trial, and larger cohort data on its toxicity had not yet been published

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Peritoneal Mesothelioma, Cytoreductive Surgery, HIPEC, Unresectable, Cisplatin, Pemetrexed (Alimta), Prognosis.

Related studies

• Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: An international survey study — M. Nowacki, M. Alyami, et al. (2018)
• Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study — O. Sgarbura, M. Hübner, et al. (2019)
• Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial — P.S. Kok, P.M. Forde, et al. (2022)
• NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma — V.D. Haakensen, A.K. Nowak, et al. (2021)
• A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma — V. Rusch, L. Saltz, et al. (1994)
• Randomized trial of intravenous versus bidirectional chemotherapy after cytoreductive surgery for malignant peritoneal mesothelioma — P.H. Sugarbaker (2023)

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