A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma

Our plain-English summary of A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma, by A.K. Nowak, C. Brown, M.J. Millward, et al (Lung Cancer, 2013).

The study

• Authors: A.K. Nowak, C. Brown, M.J. Millward, J. Creaney, M.J. Byrne, B. Hughes, G. Kremmidiotis, D.C. Bibby, A.F. Leske, P.L.R. Mitchell, N. Pavlakis, M. Boyer, M.R. Stockler
• Journal: Lung Cancer
• Published: 2013;81(3):422-427
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM. Participants had progressive MPM after first line pemetrexed/platinum chemotherapy, ECOG PS 0-1, adequate organ function, and measurable disease. BNC105P 16 mg/m(2) was administered intravenously on day 1 and 8 every 21 days until progression or undue toxicity. The primary endpoint was centrally reviewed objective response rate (RR). Tumour response was assessed every two cycles using modified RECIST. 30 patients were enrolled in 10 months, predominantly male (90%), ECOG PS 1 (77%), epithelioid histology (67%), and non-metastatic disease (67%). All patients received at least one dose of study drug, with a median of 2 cycles. No significant haematologic, biochemical, or cardiac adverse events (AEs) were observed. Grade 3 or 4 AEs occurred in 10 patients (33%). There were 2 deaths on study: 1 cardiorespiratory, the other to pneumonia. We observed 1 partial response (3%); 13 patients had stable disease (43%). Median progression free survival was 1.5 months (95% CI 1.4-2.4); median overall survival was 8.2 months (95% CI 3.8-11.9). BNC105P was safe and tolerable. The sole response was insufficient to warrant further research as a single agent.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

In plain English

This phase II, single-arm, non-randomised trial in Australia tested BNC105P as second-line treatment for malignant pleural mesothelioma. BNC105P is an experimental drug designed to disrupt tumour blood vessels. Thirty patients enrolled from July 2010 to April 2011 had cancer that had progressed after first-line pemetrexed and platinum chemotherapy; 90% were male. Patients received 16 mg/m2 by vein on days 1 and 8 of each 21-day cycle. One patient had a partial response (objective response rate 3%, 95% CI 1 to 17), none had complete responses, and 13 of 30 (43%) had stable disease. Median progression-free survival was 1.6 months (95% CI 1.4 to 2.4; the abstract says 1.5) and median overall survival 8.2 months (95% CI 3.8 to 11.9). Grade 3 or 4 adverse events, whether or not attributed to the drug, occurred in 10 patients (33%). Two patients died: one after a drug-related stroke, a death judged most likely cardio-respiratory, and one from pneumonia, judged unrelated. The authors concluded the drug was tolerable but that the results do not support its use alone in this disease.

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: Prospective, multicentre, non-randomised (single-arm) phase II clinical trial using a Simon two-stage design
• Who was studied: 30 patients with malignant pleural mesothelioma that had progressed after first-line pemetrexed/platinum chemotherapy, enrolled July 2010 to April 2011 through the Australasian Lung Cancer Trials Group; median age 64 (range 41 to 82); 27 (90%) male
• Exposure: The study treatment was the drug BNC105P, 16 mg/m2 given intravenously on days 1 and 8 of a 21-day cycle. No asbestos exposure was studied.
• Main results:
  • Recruitment was stopped after review of tumour responses in the first 24 patients; results for all 30 are reported
  • One partial response among 30 patients, with no complete responses: objective response rate 3% (95% CI 1 to 17)
  • Stable disease in 13 of 30 patients (43%)
  • In the results section, median progression-free survival was 1.6 months (95% CI 1.4 to 2.4) and median overall survival was 8.2 months (95% CI 3.8 to 11.9) for all 30 patients
  • The article's abstract gives median progression-free survival as 1.5 months (95% CI 1.4 to 2.4)
  • Grade 3 or 4 adverse events occurred in 10 of 30 patients (33%)
  • Adverse events were reported whether or not they were attributed to the study drug
  • Four patients (13%) had grade 3 or 4 fatigue
  • Nine patients had at least one serious adverse event and two patients died during the study
  • One death followed a grade 3 stroke judged related to the drug. Investigators assessed the death as most likely cardio-respiratory, but its cause could not be definitively determined.
  • The second death was from pneumonia and acute respiratory failure and was considered unrelated to the drug
  • Change in tumour measurement correlated with change in blood mesothelin concentration during treatment (rp = 0.475; p = 0.012)
• The authors' conclusion: The authors concluded that the study confirmed the drug's tolerability, but that the results do not support using BNC105P as a single agent in malignant pleural mesothelioma
• Limitations the authors state:
  • Central review of scans was not done in real time; most patients had already left the study for progression before central review results were available
  • With only one partial response, the biomarker changes showed no clear relationship with how well the drug worked
  • p-values for the 62 exploratory biomarkers were not adjusted for multiple comparisons

Topics

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

Medical terms in this study, explained in our Lexicon: Clinical Trial, Chemotherapy, Pleural Mesothelioma, Pemetrexed (Alimta), Modified RECIST (mRECIST), Epithelioid, Histology, Median Overall Survival.

Related studies

• A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma — A.K. Nowak, M.J. Millward, et al. (2012)
• A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma — W.S. Lam, J. Creaney, et al. (2020)
• 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)
• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)
• Phase II trial of ZD0473 as second-line therapy in mesothelioma — G. Giaccone, M.E. O'Brien, et al. (2002)
• 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)

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