title: A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma.
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.
authors.affiliation: Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA 6009, Australia; School of Medicine and Pharmacology, University of Western Australia, M503 35 Stirling Hwy, Crawley, WA 6009, Australia; National Centre for Asbestos Related Diseases, M503 35 Stirling Hwy, Crawley, WA 6009, Australia. Electronic address: anna.nowak@uwa.edu.au.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Medical Foundation Building, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.affiliation: Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA 6009, Australia; School of Medicine and Pharmacology, University of Western Australia, M503 35 Stirling Hwy, Crawley, WA 6009, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Millward
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, M503 35 Stirling Hwy, Crawley, WA 6009, Australia; National Centre for Asbestos Related Diseases, M503 35 Stirling Hwy, Crawley, WA 6009, Australia.
authors.forename: Jenette
authors.initials: J
authors.lastname: Creaney
authors.affiliation: Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA 6009, Australia; School of Medicine and Pharmacology, University of Western Australia, M503 35 Stirling Hwy, Crawley, WA 6009, Australia; National Centre for Asbestos Related Diseases, M503 35 Stirling Hwy, Crawley, WA 6009, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Byrne
authors.affiliation: The Prince Charles Hospital, Rode Road, Chermside, Queensland 4032, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Hughes
authors.affiliation: Bionomics Limited, 31 Dalgleish Street, Thebarton, SA 5031, Australia.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kremmidiotis
authors.affiliation: Bionomics Limited, 31 Dalgleish Street, Thebarton, SA 5031, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Bibby
authors.affiliation: Bionomics Limited, 31 Dalgleish Street, Thebarton, SA 5031, Australia.
authors.forename: Annabell F
authors.initials: AF
authors.lastname: Leske
authors.affiliation: Austin-Ludwig Medical Oncology Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia.
authors.forename: Paul L R
authors.initials: PLR
authors.lastname: Mitchell
authors.affiliation: Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia; Faculty of Medicine, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.affiliation: Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyer
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Medical Foundation Building, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stockler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D011859:Radiography; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; C568089:BNC 105P; D001572:Benzofurans; D015415:Biomarkers; D058851:GPI-Linked Proteins; D010755:Organophosphates; D050257:Tubulin Modulators; D000090204:Mesothelin
keywords: BNC105P; Biomarkers; Clinical trial; Mesothelioma; Phase II; Vascular Disrupting Agent