drugset / Trial / NCT01703507
Phase I Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma
Phase 1
Completed
17 enrolled
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
Bristol-Myers Squibb · collab
Non-randomizedParallel-groupOpen-labelTreatment
Summary
This phase I trial studies the side effects and best dose of ipilimumab when given together with whole brain radiation therapy or stereotactic radiosurgery in treating patients with melanoma with brain metastases. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find Tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy, such uses high-energy x-rays and other types of radiation to kill tumor cells. Giving radiation therapy in different ways may kill more tumor cells. Giving ipilimumab together with whole-brain radiation therapy or stereotactic radiosurgery may kill more tumor cells.
Timeline
- Start
- 2012-11-09
- Primary completion
- 2015-05-20
- Completion
- 2018-04-11
Publications
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- Background Meyners T, Heisterkamp C, Kueter JD, Veninga T, Stalpers LJ, Schild SE, Rades D. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis. BMC Cancer. 2010 Oct 26;10:582. doi: 10.1186/1471-2407-10-582.
- Background Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.
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- Background Powell JW, Chung CT, Shah HR, Canute GW, Hodge CJ, Bassano DA, Liu L, Mitchell L, Hahn SS. Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma. J Neurosurg. 2008 Dec;109 Suppl:122-8. doi: 10.3171/JNS/2008/109/12/S19.
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- Background Moschos SJ, Edington HD, Land SR, Rao UN, Jukic D, Shipe-Spotloe J, Kirkwood JM. Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol. 2006 Jul 1;24(19):3164-71. doi: 10.1200/JCO.2005.05.2498.
- Background Peggs KS, Quezada SA, Korman AJ, Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol. 2006 Apr;18(2):206-13. doi: 10.1016/j.coi.2006.01.011. Epub 2006 Feb 7.
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- Background Robert C, Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist. 2009 Aug;14(8):848-61. doi: 10.1634/theoncologist.2009-0028. Epub 2009 Aug 1.
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- Background Kaehler KC, Piel S, Livingstone E, Schilling B, Hauschild A, Schadendorf D. Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol. 2010 Oct;37(5):485-98. doi: 10.1053/j.seminoncol.2010.09.003.
- Background Morse MA. Technology evaluation: ipilimumab, Medarex/Bristol-Myers Squibb. Curr Opin Mol Ther. 2005 Dec;7(6):588-97.
- Background Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
- Background Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, Snively J, Hersh E. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008 Dec 20;26(36):5950-6. doi: 10.1200/JCO.2008.16.1927. Epub 2008 Nov 17.
- Background Schartz NE, Farges C, Madelaine I, Bruzzoni H, Calvo F, Hoos A, Lebbe C. Complete regression of a previously untreated melanoma brain metastasis with ipilimumab. Melanoma Res. 2010 Jun;20(3):247-50. doi: 10.1097/CMR.0b013e3283364a37.
- Background Hodi FS, Oble DA, Drappatz J, Velazquez EF, Ramaiya N, Ramakrishna N, Day AL, Kruse A, Mac Rae S, Hoos A, Mihm M. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. Nat Clin Pract Oncol. 2008 Sep;5(9):557-61. doi: 10.1038/ncponc1183. Epub 2008 Jul 29.
- Background Pilones KA, Kawashima N, Yang AM, Babb JS, Formenti SC, Demaria S. Invariant natural killer T cells regulate breast cancer response to radiation and CTLA-4 blockade. Clin Cancer Res. 2009 Jan 15;15(2):597-606. doi: 10.1158/1078-0432.CCR-08-1277.
- Background Jaber SH, Cowen EW, Haworth LR, Booher SL, Berman DM, Rosenberg SA, Hwang ST. Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent. Arch Dermatol. 2006 Feb;142(2):166-72. doi: 10.1001/archderm.142.2.166.
- Background Robinson MR, Chan CC, Yang JC, Rubin BI, Gracia GJ, Sen HN, Csaky KG, Rosenberg SA. Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis. J Immunother. 2004 Nov-Dec;27(6):478-9. doi: 10.1097/00002371-200411000-00008.
- Background Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A, Lautz D, Russell S, Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, Allison JP, Mihm MC, Dranoff G. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3005-10. doi: 10.1073/pnas.0712237105. Epub 2008 Feb 19.
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- Background Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008 Feb 1;26(4):527-34. doi: 10.1200/JCO.2007.12.7837.
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- Background Suh JH, Videtic GM, Aref AM, Germano I, Goldsmith BJ, Imperato JP, Marcus KJ, McDermott MW, McDonald MW, Patchell RA, Robins HI, Rogers CL, Wolfson AH, Wippold FJ 2nd, Gaspar LE. ACR Appropriateness Criteria: single brain metastasis. Curr Probl Cancer. 2010 May-Jun;34(3):162-74. doi: 10.1016/j.currproblcancer.2010.04.003.
- Background Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):291-8. doi: 10.1016/s0360-3016(99)00507-6.
- Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Williams NL, Wuthrick EJ, Kim H, Palmer JD, Garg S, Eldredge-Hindy H, Daskalakis C, Feeney KJ, Mastrangelo MJ, Kim LJ, Sato T, Kendra KL, Olencki T, Liebner DA, Farrell CJ, Evans JJ, Judy KD, Andrews DW, Dicker AP, Werner-Wasik M, Shi W. Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases. Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):22-30. doi: 10.1016/j.ijrobp.2017.05.028. Epub 2017 May 26.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ipilimumab | Monoclonal antibody | 3 mg/kg | Intravenous |
| Subject | Ipilimumab | Monoclonal antibody | 10 mg/kg | Intravenous |