Study of Re-irradiation at Relapse Versus RT and Multiple Elective rt Courses

Summary

Prospective, non-blinded, randomised two cohorts study on the efficacy of two different radiotherapy schedule for DIPG by using the same concomitant and post-radiotherapy systemic treatment.

Timeline

Start

2015-11-02

Primary completion

2022-11-11

Completion

2024-11-02

Publications

• Background Bode U, Buchen S, Warmuth-Metz M, Pietsch T, Bach F, Fleischhack G. Final report of a phase II trial of nimotuzumab in the treatment of refractory and relapsed high-grade gliomas in children and adolescents [abstract]. J Clin Oncol (2007); 25(Suppl. 2006)
• Results Bartels U, Wolff J, Gore L, Dunkel I, Gilheeney S, Allen J, Goldman S, Yalon M, Packer RJ, Korones DN, Smith A, Cohen K, Kuttesch J, Strother D, Baruchel S, Gammon J, Kowalski M, Bouffet E. Phase 2 study of safety and efficacy of nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma. Neuro Oncol. 2014 Nov;16(11):1554-9. doi: 10.1093/neuonc/nou091. Epub 2014 May 20.
• Results Bernier-Chastagner V, Grill J, Doz F, Bracard S, Gentet JC, Marie-Cardine A, Luporsi E, Margueritte G, Lejars O, Laithier V, Mechinaud F, Millot F, Kalifa C, Chastagner P. Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: results of a French Society of Paediatric Oncology Phase II Study. Cancer. 2005 Dec 15;104(12):2792-7. doi: 10.1002/cncr.21534.
• Results Bode U, Massimino M, Bach F, Zimmermann M, Khuhlaeva E, Westphal M, Fleischhack G. Nimotuzumab treatment of malignant gliomas. Expert Opin Biol Ther. 2012 Dec;12(12):1649-59. doi: 10.1517/14712598.2012.733367. Epub 2012 Oct 8.
• Results Clerk-Lamalice O, Reddick WE, Li X, Li Y, Edwards A, Glass JO, Patay Z. MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma. AJNR Am J Neuroradiol. 2016 Oct;37(10):1930-1937. doi: 10.3174/ajnr.A4814. Epub 2016 May 19.
• Results Conway AE, Reddick WE, Li Y, Yuan Y, Glass JO, Baker JN, Kun LE, Broniscer A, Patay Z. "Occult" post-contrast signal enhancement in pediatric diffuse intrinsic pontine glioma is the MRI marker of angiogenesis? Neuroradiology. 2014 May;56(5):405-12. doi: 10.1007/s00234-014-1348-9. Epub 2014 Mar 14.
• Results Lobel U, Sedlacik J, Reddick WE, Kocak M, Ji Q, Broniscer A, Hillenbrand CM, Patay Z. Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging analysis of T2 hypointense lesion components in pediatric diffuse intrinsic pontine glioma. AJNR Am J Neuroradiol. 2011 Feb;32(2):315-22. doi: 10.3174/ajnr.A2277. Epub 2010 Nov 18.
• Results Hargrave D, Chuang N, Bouffet E. Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol. 2008 Feb;86(3):313-9. doi: 10.1007/s11060-007-9473-5. Epub 2007 Oct 2.
• Results Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, Heymans MW, Warmuth-Metz M, Hargrave D, van der Hoeven EJ, Gidding CE, de Bont ES, Eshghi OS, Reddingius R, Peeters CM, Schouten-van Meeteren AY, Gooskens RH, Granzen B, Paardekooper GM, Janssens GO, Noske DP, Barkhof F, Kramm CM, Vandertop WP, Kaspers GJ, van Vuurden DG. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro Oncol. 2015 Jan;17(1):160-6. doi: 10.1093/neuonc/nou104. Epub 2014 Jun 5.
• Results Poussaint TY, Kocak M, Vajapeyam S, Packer RI, Robertson RL, Geyer R, Haas-Kogan D, Pollack IF, Vezina G, Zimmerman R, Cha S, Patay Z, Boyett JM, Kun LE. MRI as a central component of clinical trials analysis in brainstem glioma: a report from the Pediatric Brain Tumor Consortium (PBTC). Neuro Oncol. 2011 Apr;13(4):417-27. doi: 10.1093/neuonc/noq200. Epub 2011 Feb 4.
• Results Zaghloul MS, Eldebawy E, Ahmed S, Mousa AG, Amin A, Refaat A, Zaky I, Elkhateeb N, Sabry M. Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial. Radiother Oncol. 2014 Apr;111(1):35-40. doi: 10.1016/j.radonc.2014.01.013. Epub 2014 Feb 20.
• Results Wolff JE, Westphal S, Molenkamp G, Gnekow A, Warmuth-Metz M, Rating D, Kuehl J. Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer. 2002 Oct 21;87(9):945-9. doi: 10.1038/sj.bjc.6600552.
• Results Wolff JE, Wagner S, Reinert C, Gnekow A, Kortmann RD, Kuhl J, Van Gool SW. Maintenance treatment with interferon-gamma and low-dose cyclophosphamide for pediatric high-grade glioma. J Neurooncol. 2006 Sep;79(3):315-21. doi: 10.1007/s11060-006-9147-8. Epub 2006 Apr 28.
• Results Wolff JE, Kortmann RD, Wolff B, Pietsch T, Peters O, Schmid HJ, Rutkowski S, Warmuth-Metz M, Kramm C. High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study. J Neurooncol. 2011 May;102(3):433-42. doi: 10.1007/s11060-010-0334-2. Epub 2010 Aug 8.
• Results Wolff JE, Driever PH, Erdlenbruch B, Kortmann RD, Rutkowski S, Pietsch T, Parker C, Metz MW, Gnekow A, Kramm CM. Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol. Cancer. 2010 Feb 1;116(3):705-12. doi: 10.1002/cncr.24730.
• Results Wagner S, Warmuth-Metz M, Emser A, Gnekow AK, Strater R, Rutkowski S, Jorch N, Schmid HJ, Berthold F, Graf N, Kortmann RD, Pietsch T, Sorensen N, Peters O, Wolff JE. Treatment options in childhood pontine gliomas. J Neurooncol. 2006 Sep;79(3):281-7. doi: 10.1007/s11060-006-9133-1. Epub 2006 Apr 6.
• Results Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
• Results Sufit A, Donson AM, Birks DK, Knipstein JA, Fenton LZ, Jedlicka P, Hankinson TC, Handler MH, Foreman NK. Diffuse intrinsic pontine tumors: a study of primitive neuroectodermal tumors versus the more common diffuse intrinsic pontine gliomas. J Neurosurg Pediatr. 2012 Aug;10(2):81-8. doi: 10.3171/2012.3.PEDS11316. Epub 2012 Jun 29.
• Results Bogaerts J, Sydes MR, Keat N, McConnell A, Benson A, Ho A, Roth A, Fortpied C, Eng C, Peckitt C, Coens C, Pettaway C, Arnold D, Hall E, Marshall E, Sclafani F, Hatcher H, Earl H, Ray-Coquard I, Paul J, Blay JY, Whelan J, Panageas K, Wheatley K, Harrington K, Licitra L, Billingham L, Hensley M, McCabe M, Patel PM, Carvajal R, Wilson R, Glynne-Jones R, McWilliams R, Leyvraz S, Rao S, Nicholson S, Filiaci V, Negrouk A, Lacombe D, Dupont E, Pauporte I, Welch JJ, Law K, Trimble T, Seymour M. Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative. Eur J Cancer. 2015 Feb;51(3):271-81. doi: 10.1016/j.ejca.2014.10.027. Epub 2014 Dec 24.
• Results Chen K, Shan M. Optimal and minimax three-stage designs for phase II oncology clinical trials. Contemp Clin Trials. 2008 Jan;29(1):32-41. doi: 10.1016/j.cct.2007.04.008. Epub 2007 May 6.
• Results Rutka JT. Biopsy of diffuse intrinsic pontine gliomas? J Neurosurg Pediatr. 2012 Aug;10(2):79-80. doi: 10.3171/2012.2.PEDS1237. Epub 2012 Jun 29. No abstract available.
• Results Roujeau T, Machado G, Garnett MR, Miquel C, Puget S, Geoerger B, Grill J, Boddaert N, Di Rocco F, Zerah M, Sainte-Rose C. Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg. 2007 Jul;107(1 Suppl):1-4. doi: 10.3171/PED-07/07/001.
• Results Pollack IF, Stewart CF, Kocak M, Poussaint TY, Broniscer A, Banerjee A, Douglas JG, Kun LE, Boyett JM, Geyer JR. A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas: a report from the Pediatric Brain Tumor Consortium. Neuro Oncol. 2011 Mar;13(3):290-7. doi: 10.1093/neuonc/noq199. Epub 2011 Feb 3.
• Results Packer RJ, Krailo M, Mehta M, Warren K, Allen J, Jakacki R, Villablanca JG, Chiba A, Reaman G. Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas. Cancer. 2005 Sep 15;104(6):1281-7. doi: 10.1002/cncr.21301.
• Results Negretti L, Bouchireb K, Levy-Piedbois C, Habrand JL, Dhermain F, Kalifa C, Grill J, Dufour C. Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience. J Neurooncol. 2011 Sep;104(3):773-7. doi: 10.1007/s11060-011-0542-4. Epub 2011 Feb 17.
• Results Massimino M, Spreafico F, Biassoni V, Simonetti F, Riva D, Trecate G, Giombini S, Poggi G, Pecori E, Pignoli E, Casanova M, Ferrari A, Meazza C, Luksch R, Terenziani M, Cefalo G, Podda M, Polastri D, Clerici CA, Fossati-Bellani F, Gandola L. Diffuse pontine gliomas in children: changing strategies, changing results? A mono-institutional 20-year experience. J Neurooncol. 2008 May;87(3):355-61. doi: 10.1007/s11060-008-9525-5. Epub 2008 Jan 24.
• Results Massimino M, Bode U, Biassoni V, Fleischhack G. Nimotuzumab for pediatric diffuse intrinsic pontine gliomas. Expert Opin Biol Ther. 2011 Feb;11(2):247-56. doi: 10.1517/14712598.2011.546341. Epub 2010 Dec 21.
• Results Massimino M, Biassoni V, Miceli R, Schiavello E, Warmuth-Metz M, Modena P, Casanova M, Pecori E, Giangaspero F, Antonelli M, Buttarelli FR, Potepan P, Pollo B, Nunziata R, Spreafico F, Podda M, Anichini A, Clerici CA, Sardi I, De Cecco L, Bode U, Bach F, Gandola L. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol. 2014 Jun;118(2):305-312. doi: 10.1007/s11060-014-1428-z. Epub 2014 Apr 3.
• Results MacDonald TJ. Diffuse intrinsic pontine glioma (DIPG): time to biopsy again? Pediatr Blood Cancer. 2012 Apr;58(4):487-8. doi: 10.1002/pbc.24090. No abstract available.
• Results Lassman LP, Arjona VE. Pontine gliomas of childhood. Lancet. 1967 Apr 29;1(7496):913-5. doi: 10.1016/s0140-6736(67)91485-7. No abstract available.
• Results Kretschmar CS, Tarbell NJ, Barnes PD, Krischer JP, Burger PC, Kun L. Pre-irradiation chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors. A phase II study of the Pediatric Oncology Group, Protocol 8833. Cancer. 1993 Aug 15;72(4):1404-13. doi: 10.1002/1097-0142(19930815)72:43.0.co;2-g.
• Results Jennings MT, Sposto R, Boyett JM, Vezina LG, Holmes E, Berger MS, Bruggers CS, Bruner JM, Chan KW, Dusenbery KE, Ettinger LJ, Fitz CR, Lafond D, Mandelbaum DE, Massey V, McGuire W, McNeely L, Moulton T, Pollack IF, Shen V. Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol. 2002 Aug 15;20(16):3431-7. doi: 10.1200/JCO.2002.04.109.
• Results Jennings MT, Freeman ML, Murray MJ. Strategies in the treatment of diffuse pontine gliomas: the therapeutic role of hyperfractionated radiotherapy and chemotherapy. J Neurooncol. 1996 May-Jun;28(2-3):207-22. doi: 10.1007/BF00250200.
• Results Janssens GO, Gidding CE, Van Lindert EJ, Oldenburger FR, Erasmus CE, Schouten-Meeteren AY, Kaanders JH. The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):722-6. doi: 10.1016/j.ijrobp.2008.05.030. Epub 2008 Nov 5.
• Results Jackson S, Patay Z, Howarth R, Pai Panandiker AS, Onar-Thomas A, Gajjar A, Broniscer A. Clinico-radiologic characteristics of long-term survivors of diffuse intrinsic pontine glioma. J Neurooncol. 2013 Sep;114(3):339-44. doi: 10.1007/s11060-013-1189-0. Epub 2013 Jun 29.
• Results Ivanova A, Qaqish BF, Schell MJ. Continuous toxicity monitoring in phase II trials in oncology. Biometrics. 2005 Jun;61(2):540-5. doi: 10.1111/j.1541-0420.2005.00311.x.
• Results Harris W. A Case of Pontine Glioma, with Special Reference to the Paths of Gustatory Sensation. Proc R Soc Med. 1926;19(Neurol Sect):1-5. doi: 10.1177/003591572601900901. No abstract available.
• Results Hargrave D, Bartels U, Bouffet E. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006 Mar;7(3):241-8. doi: 10.1016/S1470-2045(06)70615-5.
• Results Gilbertson RJ, Hill DA, Hernan R, Kocak M, Geyer R, Olson J, Gajjar A, Rush L, Hamilton RL, Finkelstein SD, Pollack IF. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3620-4.
• Results Geyer JR, Stewart CF, Kocak M, Broniscer A, Phillips P, Douglas JG, Blaney SM, Packer RJ, Gururangan S, Banerjee A, Kieran MW, Kun LE, Gilbertson RJ, Boyett JM. A phase I and biology study of gefitinib and radiation in children with newly diagnosed brain stem gliomas or supratentorial malignant gliomas. Eur J Cancer. 2010 Dec;46(18):3287-93. doi: 10.1016/j.ejca.2010.07.005. Epub 2010 Aug 12.
• Results Geoerger B, Hargrave D, Thomas F, Ndiaye A, Frappaz D, Andreiuolo F, Varlet P, Aerts I, Riccardi R, Jaspan T, Chatelut E, Le Deley MC, Paoletti X, Saint-Rose C, Leblond P, Morland B, Gentet JC, Meresse V, Vassal G; ITCC (Innovative Therapies for Children with Cancer) European Consortium. Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors. Neuro Oncol. 2011 Jan;13(1):109-18. doi: 10.1093/neuonc/noq141. Epub 2010 Oct 25.
• Results Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):265-71. doi: 10.1016/s0360-3016(97)00572-5.
• Results Frappaz D, Schell M, Thiesse P, Marec-Berard P, Mottolese C, Perol D, Bergeron C, Philip T, Ricci AC, Galand-Desme S, Szathmari A, Carrie C. Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol. 2008 Aug;10(4):599-607. doi: 10.1215/15228517-2008-029. Epub 2008 Jun 24.
• Results Fontanilla HP, Pinnix CC, Ketonen LM, Woo SY, Vats TS, Rytting ME, Wolff JE, Mahajan A. Palliative reirradiation for progressive diffuse intrinsic pontine glioma. Am J Clin Oncol. 2012 Feb;35(1):51-7. doi: 10.1097/COC.0b013e318201a2b7.
• Results Feshchenko EA, Langdon WY, Tsygankov AY. Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine residues that become phosphorylated in activated T cells. J Biol Chem. 1998 Apr 3;273(14):8323-31. doi: 10.1074/jbc.273.14.8323.
• Results Doz F, Neuenschwander S, Bouffet E, Gentet JC, Schneider P, Kalifa C, Mechinaud F, Chastagner P, De Lumley L, Sariban E, Plantaz D, Mosseri V, Bours D, Alapetite C, Zucker JM. Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Societe Francaise d'Oncologie Pediatrique. Eur J Cancer. 2002 Apr;38(6):815-9. doi: 10.1016/s0959-8049(02)00029-1.
• Results Bradley KA, Zhou T, McNall-Knapp RY, Jakacki RI, Levy AS, Vezina G, Pollack IF. Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children's oncology group phase 2 study. Int J Radiat Oncol Biol Phys. 2013 Jan 1;85(1):e55-60. doi: 10.1016/j.ijrobp.2012.09.004. Epub 2012 Oct 22.
• Results Broniscer A, Baker JN, Tagen M, Onar-Thomas A, Gilbertson RJ, Davidoff AM, Pai Panandiker AS, Leung W, Chin TK, Stewart CF, Kocak M, Rowland C, Merchant TE, Kaste SC, Gajjar A. Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol. 2010 Nov 1;28(31):4762-8. doi: 10.1200/JCO.2010.30.3545. Epub 2010 Oct 4.
• Results Broniscer A, Baker SJ, Stewart CF, Merchant TE, Laningham FH, Schaiquevich P, Kocak M, Morris EB, Endersby R, Ellison DW, Gajjar A. Phase I and pharmacokinetic studies of erlotinib administered concurrently with radiotherapy for children, adolescents, and young adults with high-grade glioma. Clin Cancer Res. 2009 Jan 15;15(2):701-7. doi: 10.1158/1078-0432.CCR-08-1923.
• Results Boop FA. Brainstem gliomas. J Neurosurg Pediatr. 2011 Dec;8(6):537-8; discussion 538. doi: 10.3171/2011.8.PEDS11310. No abstract available.
• Results Memorial Sloan-Kettering Cancer Center. External beam radiation therapy and cetuximab followed by irinotecan and cetuximab for children and young adults with newly diagnosed diffuse pontine tumors and high-grade astrocytomas (POE08-01). ClinicalTrials. gov identifier NCT01012609
• Results Fleischhack G, Siegler N, Zimmermann M, et al. Concomitant therapy of nimotuzumab and standard radiotherapy for the treatment of newly diagnosed diffuse intrinsic pontine gliomas in children and adolescents. 14th international symposium of pediatric neuro-oncology, Vienna, Austria 20-23 June 2010
• Results Broniscer A, Baker SD, Wetmore C, Pai Panandiker AS, Huang J, Davidoff AM, Onar-Thomas A, Panetta JC, Chin TK, Merchant TE, Baker JN, Kaste SC, Gajjar A, Stewart CF. Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. Clin Cancer Res. 2013 Jun 1;19(11):3050-8. doi: 10.1158/1078-0432.CCR-13-0306. Epub 2013 Mar 27.

Drugs

Indications