Rationale and design of the 500-patient, 3-year, and prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry

Kevin O Lillehei, Steven N Kalkanis, Linda M Liau, Dellann Elliott Mydland, Jeffrey Olson, Nina A Paleologos, Timothy Ryken, Tania Johnson, Evan Scullin, Kevin O Lillehei, Steven N Kalkanis, Linda M Liau, Dellann Elliott Mydland, Jeffrey Olson, Nina A Paleologos, Timothy Ryken, Tania Johnson, Evan Scullin

Abstract

Implantation of biodegradable wafers impregnated with carmustine (BCNU) is one of the few chemotherapeutic modalities that have been evaluated in Phase III trials and approved by the US FDA for treatment of newly diagnosed high-grade glioma and recurrent glioblastoma. Enrolling up to 500 patients for 3-year follow-up at over 30 sites, the prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) will evaluate BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular tumor analysis. Subgroup analyses will include tumor type, molecular marker status, and treatment combinations. Interim analyses from the VIGILANT registry will be reported until complete results are available in 2024.

Keywords: BCNU wafers; chemotherapy; glioblastoma; high-grade glioma; multimodality; patterns of care; study protocol.

Conflict of interest statement

Financial & competing interests disclosure

The VIGILANT registry is funded by Arbor Pharmaceuticals, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors wish to thank the representatives of Galen Press, Inc., for editorial and administrative support in preparation of this manuscript. Funding support for Galen Press was provided by Arbor Pharmaceuticals.

Figures

Figure 1. . Schematic drawing of biodegradable…
Figure 1.. Schematic drawing of biodegradable wafers impregnated with carmustine.
The BCNU wafer releases BCNU at a constant rate over a period of a week. Transport into the tissue adjacent to the implant occurs primarily by diffusion, which is augmented immediately postresection by convective transport with interstitial flow resulting from vasogenic edema. More than 70% of the copolymer degrades by 3 weeks [2]. BCNU: 1,3-bis(2-chloroethyl)-1-nitrosourea.
Figure 2. . The Vigilant ObservatIon of…
Figure 2.. The Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry trial schematic.
BCNU: 1,3-bis(2-chloroethyl)-1-nitrosourea.

References

    1. Wait SD, Prabhu RS, Burri SH, Atkins TG, Asher AL. Polymeric drug delivery for the treatment of glioblastoma. Neuro Oncol. 2015;17(Suppl. 2):ii9–ii23.
    1. Fleming AB, Saltzman WM. Pharmacokinetics of the carmustine implant. Clin. Pharmacokinet. 2002;41(6):403–419.
    1. Brem H, Mahaley MS, Jr, Vick NA, et al. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J. Neurosurg. 1991;74(3):441–446.
    1. Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002;359(9311):1011–1018.
    1. Drapeau A, Fortin D. Chemotherapy delivery strategies to the central nervous system: neither optional nor superfluous. Curr. Cancer Drug Targets. 2015;15(9):752–768.
    1. Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 1995;345(8956):1008–1012.
    1. Valtonen S, Timonen U, Toivanen P, et al. Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery. 1997;41(1):44–48. discussion 48–49.
    1. Westphal M, Hilt DC, Bortey E, et al. A Phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79–88.
    1. Westphal M, Ram Z, Riddle V, Hilt D, Bortey E. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir. (Wien) 2006;148(3):269–275. discussion 275.
    1. Walker MD, Alexander E, Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J. Neurosurg. 1978;49(3):333–343.
    1. Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev. Anticancer Ther. 2006;6(8):1187–1204.
    1. Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14(11):1131–1138.
    1. Stupp R, Mason WP, Van Den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005;352(10):987–996.
    1. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised Phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–466.
    1. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 2014;370(8):699–708.
    1. Gilbert MR, Sulman EP, Mehta MP. Bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 2014;370(21):2048–2049.
    1. Stupp R, Hegi ME, Gorlia T, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, Phase 3 trial. Lancet Oncol. 2014;15(10):1100–1108.
    1. Ashby LS, Smith KA, Stea B. Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review. World J. Surg. Oncol. 2016;14(1):225.
    1. Xing WK, Shao C, Qi ZY, Yang C, Wang Z. The role of Gliadel wafers in the treatment of newly diagnosed GBM: a meta-analysis. Drug Des. Devel. Ther. 2015;9:3341–3348.
    1. Chowdhary SA, Ryken T, Newton HB. Survival outcomes and safety of carmustine wafers in the treatment of high-grade gliomas: a meta-analysis. J. Neurooncol. 2015;122(2):367–382.
    1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–820.
    1. Zou P, Xu H, Chen P, et al. IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS ONE. 2013;8(7):e68782.
    1. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 2005;352(10):997–1003.
    1. Gorlia T, Van Den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE.3. Lancet Oncol. 2008;9(1):29–38.
    1. Van Den Bent MJ, Weller M, Wen PY, Kros JM, Aldape K, Chang S. A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics. Neuro Oncol. 2017;19(5):614–624.
    1. Gorlia T, Delattre JY, Brandes AA, et al. New clinical, pathological and molecular prognostic models and calculators in patients with locally diagnosed anaplastic oligodendroglioma or oligoastrocytoma. A prognostic factor analysis of European Organisation for Research and Treatment of Cancer Brain Tumour Group Study 26951. Eur. J. Cancer. 2013;49(16):3477–3485.
    1. Padfield E, Ellis HP, Kurian KM. Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma. Front. Oncol. 2015;5:5.
    1. Aoki T, Nishikawa R, Sugiyama K, et al. A multicenter Phase I/II study of the BCNU implant (Gliadel((R)) Wafer) for Japanese patients with malignant gliomas. Neurol. Med. Chir. (Tokyo) 2014;54(4):290–301.
    1. Bock HC, Puchner MJ, Lohmann F, et al. First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience. Neurosurg. Rev. 2010;33(4):441–449.
    1. Burri SH, Prabhu RS, Sumrall AL, et al. BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, Phase II trial. J. Neurooncol. 2015;123(2):259–266.
    1. Duntze J, Litre CF, Eap C, et al. Implanted carmustine wafers followed by concomitant radiochemotherapy to treat newly diagnosed malignant gliomas: prospective, observational, multicenter study on 92 cases. Ann. Surg. Oncol. 2013;20(6):2065–2072.
    1. McGirt MJ, Than KD, Weingart JD, et al. Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme. J. Neurosurg. 2009;110(3):583–588.
    1. Menei P, Metellus P, Parot-Schinkel E, et al. Biodegradable carmustine wafers (Gliadel) alone or in combination with chemoradiotherapy: the French experience. Ann. Surg. Oncol. 2010;17(7):1740–1746.
    1. Miglierini P, Bouchekoua M, Rousseau B, Hieu PD, Malhaire JP, Pradier O. Impact of the peri-operatory application of GLIADEL wafers (BCNU, carmustine) in combination with temozolomide and radiotherapy in patients with glioblastoma multiforme: efficacy and toxicity. Clin. Neurol. Neurosurg. 2012;114(9):1222–1225.
    1. Noel G, Schott R, Froelich S, et al. Retrospective comparison of chemoradiotherapy followed by adjuvant chemotherapy, with or without prior gliadel implantation (carmustine) after initial surgery in patients with newly diagnosed high-grade gliomas. Int. J. Radiat. Oncol. Biol. Phys. 2012;82(2):749–755.
    1. Pan E, Mitchell SB, Tsai JS. A retrospective study of the safety of BCNU wafers with concurrent temozolomide and radiotherapy and adjuvant temozolomide for newly diagnosed glioblastoma patients. J. Neurooncol. 2008;88(3):353–357.
    1. Pavlov V, Page P, Abi-Lahoud G, et al. Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas. Br. J. Neurosurg. 2015;29(4):524–531.
    1. Salvati M, D'elia A, Frati A, Brogna C, Santoro A, Delfini R. Safety and feasibility of the adjunct of local chemotherapy with biodegradable carmustine (BCNU) wafers to the standard multimodal approach to high grade gliomas at first diagnosis. J. Neurosurg. Sci. 2011;55(1):1–6.
    1. US Department of Health. Common Terminology Criteria for Adverse Events (CTCAE) 2010. Version 4.0. Washington DC: National Institutes of Health.
    1. Hottinger AF, Pacheco P, Stupp R. Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro Oncol. 2016;18(10):1338–1349.
    1. Inda MM, Bonavia R, Mukasa A, et al. Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev. 2010;24(16):1731–1745.
    1. Arimappamagan A, Kruthika Dawn R, Paturu K, Santosh V. 332 molecular characteristics of tumor infiltrating front in glioblastoma: insights into molecular heterogeneity and implications on targeted therapy. Neurosurgery. 2016;63(Suppl. 1):197.
    1. Qazi MA, Vora P, Venugopal C, et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann. Oncol. 2017;28(7):1448–1456.
    1. Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma – are we there yet? Neuro Oncol. 2013;15(1):4–27.
    1. Ryken TC, Kalkanis SN, Buatti JM, Olson JJ. The role of cytoreductive surgery in the management of progressive glioblastoma: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 2014;118(3):479–488.
    1. Klein J, Juratli TA, Radev Y, et al. Safety and effectiveness of bis-chloroethylnitrosourea wafer chemotherapy in elderly patients with recurrent glioblastoma. Oncology. 2017;93(1):43–50.
    1. Anderson FA, Jr Glioma Outcomes Project Advisory B. The Glioma Outcomes Project: a resource for measuring and improving glioma outcomes. Neurosurg. Focus. 1998;4(6):e8.
    1. Chang SM, Parney IF, Mcdermott M, et al. Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcomes Project. J. Neurosurg. 2003;98(6):1175–1181.
    1. Laws ER, Parney IF, Huang W, et al. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J. Neurosurg. 2003;99(3):467–473.
    1. Litofsky NS, Farace E, Anderson F, Jr, et al. Depression in patients with high-grade glioma: results of the Glioma Outcomes Project. Neurosurgery. 2004;54(2):358–366. discussion 366–357.
    1. Chang SM, Parney IF, Huang W, et al. Patterns of care for adults with newly diagnosed malignant glioma. JAMA. 2005;293(5):557–564.
    1. Chang SM, Barker FG, 2nd, Schmidt MH, et al. Clinical trial participation among patients enrolled in the Glioma Outcomes Project. Cancer. 2002;94(10):2681–2687.
    1. Olson JJ, Nayak L, Ormond DR, et al. The role of targeted therapies in the management of progressive glioblastoma: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 2014;118(3):557–599.
    1. Ulmer S, Spalek K, Nabavi A, et al. Temporal changes in magnetic resonance imaging characteristics of Gliadel wafers and of the adjacent brain parenchyma. Neuro Oncol. 2012;14(4):482–490.
    1. Colen RR, Zinn PO, Hazany S, et al. Magnetic resonance imaging appearance and changes on intracavitary Gliadel wafer placement: a pilot study. World J. Radiol. 2011;3(11):266–272.
    1. Peters KB, West MJ, Hornsby WE, et al. Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients. J. Neurooncol. 2014;120(3):499–506.
    1. Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity and guidelines. J. Clin. Oncol. 1984;2(3):187–193.
    1. Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J. Clin. Oncol. 2010;28(11):1963–1972.

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