Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases

Summary

The protocol is designed to determine the efficacy of temozolomide in preventing the development of new brain metastases within the first year in patients undergoing stereotactic radiation for newly diagnosed brain metastases.

Timeline

Start

2002-07

Primary completion

2008-10

Completion

2015-06

Publications

• Background DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.
• Background Pirzkall A, Debus J, Lohr F, Fuss M, Rhein B, Engenhart-Cabillic R, Wannenmacher M. Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol. 1998 Nov;16(11):3563-9. doi: 10.1200/JCO.1998.16.11.3563.
• Background Sneed PK, Lamborn KR, Forstner JM, McDermott MW, Chang S, Park E, Gutin PH, Phillips TL, Wara WM, Larson DA. Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999 Feb 1;43(3):549-58. doi: 10.1016/s0360-3016(98)00447-7.
• Background Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998 Nov 4;280(17):1485-9. doi: 10.1001/jama.280.17.1485.
• Background Stevens MF, Hickman JA, Stone R, Gibson NW, Baig GU, Lunt E, Newton CG. Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one , a novel broad-spectrum antitumor agent. J Med Chem. 1984 Feb;27(2):196-201. doi: 10.1021/jm00368a016.
• Background Tsang LL, Quarterman CP, Gescher A, Slack JA. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemother Pharmacol. 1991;27(5):342-6. doi: 10.1007/BF00688855.
• Background Bull VL, Tisdale MJ. Antitumour imidazotetrazines--XVI. Macromolecular alkylation by 3-substituted imidazotetrazinones. Biochem Pharmacol. 1987 Oct 1;36(19):3215-20. doi: 10.1016/0006-2952(87)90636-8.
• Background Tisdale MJ. Antitumour imidazotetrazines--XVIII. Modification of the level of 5-methylcytosine in DNA by 3-substituted imidazotetrazinones. Biochem Pharmacol. 1989 Apr 1;38(7):1097-101. doi: 10.1016/0006-2952(89)90254-2.
• Background Tsang LL, Farmer PB, Gescher A, Slack JA. Characterisation of urinary metabolites of temozolomide in humans and mice and evaluation of their cytotoxicity. Cancer Chemother Pharmacol. 1990;26(6):429-36. doi: 10.1007/BF02994094.
• Background Clark AS, Stevens MF, Sansom CE, Schwalbe CH. Anti-tumour imidazotetrazines. Part XXI. Mitozolomide and temozolomide: probes for the major groove of DNA. Anticancer Drug Des. 1990 Feb;5(1):63-8.
• Background Stevens MF, Hickman JA, Langdon SP, Chubb D, Vickers L, Stone R, Baig G, Goddard C, Gibson NW, Slack JA, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res. 1987 Nov 15;47(22):5846-52.
• Background Gibson NW, Hickman JA, Erickson LC. DNA cross-linking and cytotoxicity in normal and transformed human cells treated in vitro with 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d] -1,2,3,5-tetrazin-4(3H)-one. Cancer Res. 1984 May;44(5):1772-5.
• Background Hartley JA, Gibson NW, Kohn KW, Mattes WB. DNA sequence selectivity of guanine-N7 alkylation by three antitumor chloroethylating agents. Cancer Res. 1986 Apr;46(4 Pt 2):1943-7.
• Background SN92384: SCH 52365: Pharmacokinetics of SCH 52365 in Rats Following a Single Oral Gavage or Intravenous Dose. Schering-Plough Research Institute
• Background SN92385: SCH 52365: Pharmacokinetics of SCH 52365 in Beagle Dogs Following a Single Oral Gavage or a Single Intravenous Cross-Over Study. Schering Plough Research Institute
• Background SN92131: Single-Cycle Oral Toxicity Study of SCH 52365 in Rats. Schering Plough Research Institute.
• Background SN93092: Single-Cycle Oral Toxicity Study with Lower Doses of SCH 52365 in Rats. Schering-Plough Research Institute
• Background SN92133: Three-Cycle Oral Toxicity Study of SCH 52365 in Rats. Schering Plough Research Institute.
• Background SN92132: Single-Cycle Oral Toxicity Study of SCH 52365 in Dogs. Schering-Plough Research Institute
• Background SN93093: Single-Cycle Oral Toxicity Study with Lower Doses of SCH 52365 in Dogs. Schering-Plough Research Institute
• Background SN92134: Three-Cycle Oral Toxicity Study of SCH 52365 in Dogs. Schering-Plough Research Institute
• Background SN92380: SCH 52365: Mass Balance and Excretion of 14C-SCH 52365 Following a Single Intravenous or Oral Dose in Male Rats. Schering-Plough Research Institute
• Background SN92383: SCH 52365: Absorption, Distribution and Metabolism of 14C SCH 52365 Following a Single Oral Dose in Male Rats. Schering-Plough Research Institute
• Background SN92381: SCH 52365: Absorption, Metabolism, Excretion, and Pharmacokinetics of 14C-SCH 52365 Following a Single Oral or Intravenous Dose in the Male Rat. Schering-Plough Research Institute
• Background SN92382: SCH 52365: Absorption, Metabolism, Excretion, and Pharmacokinetics of 14C-SCH 52365 Following a Single Oral And Intravenous Dose in the Male Dog. Schering-Plough Research Institute
• Background Patel M, McCully C, Godwin K, Balis FM. Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates. J Neurooncol. 2003 Feb;61(3):203-7. doi: 10.1023/a:1022592913323.
• Background Newlands ES, Blackledge GR, Slack JA, Rustin GJ, Smith DB, Stuart NS, Quarterman CP, Hoffman R, Stevens MF, Brampton MH, et al. Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). Br J Cancer. 1992 Feb;65(2):287-91. doi: 10.1038/bjc.1992.57.
• Background O'Reilly SM, Newlands ES, Stevens MFG, Brampton MH, Slack JA et al: Temozolomide (CCRG 81045; M&B 39831; NSC 362856): a new oral cytotoxic agent with activity against melanoma, mycosis fungoides and high-grade glioma. Proc. AACR. 1992; 33: A1267
• Background O'Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, et al. Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer. 1993;29A(7):940-2. doi: 10.1016/s0959-8049(05)80198-4.
• Background Data on file at the Cancer Research Campaign Data Center. Phase II trial of temozolomide in high-grade glioma. Schering-Plough Research Institute. Study No. H93-090-50).
• Background Data on file at the Cancer Research Campaign Data Center. Phase II trial of temozolomide in advanced malignant melanoma. Schering-Plough Research Institute. Study No. H93 088-50
• Background Bleehen NM, Newlands ES, Lee SM, Thatcher N, Selby P, Calvert AH, Rustin GJ, Brampton M, Stevens MF. Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol. 1995 Apr;13(4):910-3. doi: 10.1200/JCO.1995.13.4.910.
• Background Data on file at the Cancer Research Campaign Data Center. Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma. Schering-Plough Research Institute. Study No. H93-089-50).
• Background Woll PJ, Crowther D, Johnson PW, Soukop M, Harper PG, Harris M, Brampton MH, Newlands ES. Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma. Br J Cancer. 1995 Jul;72(1):183-4. doi: 10.1038/bjc.1995.299.
• Background Data on file at Schering-Plough Research Institute (I93-114-01).
• Background Brada M, Moore S, Judson I, Batra VJ, Quartey P, Dugan M: A Phase I study of SCH 52365 (temozolomide) in adult patients with advanced cancer. Proc. ASCO. 1995; 14:1521
• Background Data on file at Schering-Plough Research Institute (C94-022-01).
• Background Hammond LA, Eckardt JR, Baker SD, Eckhardt SG, Dugan M, Forral K, Reidenberg P, Statkevich P, Weiss GR, Rinaldi DA, Von Hoff DD, Rowinsky EK. Phase I and pharmacokinetic study of temozolomide on a daily-for-5-days schedule in patients with advanced solid malignancies. J Clin Oncol. 1999 Aug;17(8):2604-13. doi: 10.1200/JCO.1999.17.8.2604.
• Background Yung A, Levin VA, Albright R, Olson J, Fredericks R, Fink K, Prados M, Brada M, Spence A, Brunner J, Yue N, Dugan MH, Zaknoen S. Temodal Brain Tumor Group: Randomized trial of temodal (TEM) vs. procarbazine (PCB) in glioblastoma multi-forme (GBM) at first relapse [abstract]. Proceedings of the American Society of Clinical Oncology. 1999; 18:139a.
• Background Christodoulou C, Bafaloukos D, Kosmidis P, Samantas E, Bamias A, Papakostas P, Karabelis A, Bacoyiannis C, Skarlos DV; Hellenic Cooperative Oncology Group. Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Ann Oncol. 2001 Feb;12(2):249-54. doi: 10.1023/a:1008354323167.
• Background Paraskevaidis E, Antonadou D, Sarris G, Kolliarakis N, Economou I, Karageirgus P, Throuvalas N. A Phase II randomized trial of synchronous radiotherapy with temozolomide in brain metastases. Metaxas Cancer Hospital, Pireus, Greece
• Results Abrey JD, Olson DY, Boutros M, Mack A, Rodavitch JJ, Raizer MG. A Phase II Study of Temozolomide for Recurrent Brain Metastases. Malkin; Memorial Sloan-Kettering Cancer Center, New York, NY. Abstract 643

Drugs

Indications