@article{7e2c20e3b88f4ca387db4715cbf723ac,
title = "Phase I-II trial of imatinib mesylate (Gleevec; STI571) in treatment of recurrent oligodendroglioma and mixed oligoastrocytoma. North central cancer treatment group study N0272 (ALLIANCE/NCCTG)",
abstract = "Purpose: To evaluate the pharmacokinetics and efficacy of imatinib in patients with recurrent oligodendroglial tumors. Methods: Patients with progressive WHO grade II-III recurrent tumors after prior RT and chemotherapy were eligible. A phase I dose-escalation study was conducted for patients on enzyme-inducing anticonvulsants (EIAC). A phase II study for non-EIAC patients utilized a fixed dose of 600 mg/D. Primary efficacy endpoint was 6-month progression-free survival (PFS6). A 2-stage design was utilized, with 90% power to detect PFS6 increase from 25 to 45%. Results: In the Phase I, maximum tolerated dose was not reached at 1200 mg/D. For phase II patients, overall PFS6 was 33% and median PFS 4.0 months (95% CI 2.1, 5.7). Median overall survival (OS) was longer in imatinib-treated patients compared with controls (16.6 vs. 8.0 months; HR = 0.64, 95% CI 0.41,1.0, p = 0.049), and longer in patients with 1p/19q-codeleted tumors (19.2 vs. 6.2 months, HR = 0.43, 95% CI 0.21,0.89, p = 0.019). Confirmed response rate was 3.9% (PR = 1; REGR = 1), with stable disease observed in 52.9%. At 600 mg/D, mean steady-state imatinib plasma concentration was 2513 ng/ml (95% CI 1831,3195). Grade 3–4 adverse events (hematologic, fatigue, GI, hypophosphatemia, or hemorrhage) occurred in 61%. Conclusions: Although adequate plasma levels were achieved, the observed PFS6 of 33% did not reach our pre-defined threshold for success. Although OS was longer in imatinib-treated patients than controls, this finding would require forward validation in a larger cohort. Imatinib might show greater activity in a population enriched for PDGF-dependent pathway activation in tumor tissue.",
keywords = "Alliance, N0272, NCCTG, Oligodendroglioma, PDGF, imatinib",
author = "Jaeckle, {Kurt A.} and Anderson, {S. K.} and Twohy, {Erin L.} and Dixon, {Jesse G.} and Caterina Giannini and Robert Jenkins and Egorin, {Merrill J.} and Sarkaria, {Jann N.} and Brown, {Paul D.} and Flynn, {P. J.} and John Schwerkoske and Buckner, {Jan C.} and Evanthia Galanis",
note = "Funding Information: Imatinib was provided by the U.S. National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) under a Cooperative Research and Development Agreement with Novartis Pharmaceuticals (Florham Park, NJ), and the protocol was approved by NCI/CTEP. Participants signed an IRB-approved, protocol-specific informed consent document in accordance with federal and institutional guidelines. Site participation required protocol approval by local institutional review boards, in accordance with assurances filed with the U.S. Department of Health and Human Services. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The trial is registered in the public domain (clinicaltrials. gov; NCT00049127). Funding Information: The following institutional networks participated in this study: Cancer Alliance of Nebraska, Omaha, NE, Gamini Soori; Carle Cancer Center NCI Community Oncology Research Program, Urbana, IL, Kendrith Rowland, UG1CA189861; Geisinger Cancer Institute NCI Community Oncology Research Program, Danville, PA, Srilatha Hosur, UG1CA189847; Iowa Oncology Research Assoc.; Mayo Clinic LAPS, Rochester, MN, Steven Alberts, U10CA180790; Metro Minnesota Community Oncology Research Consortium, Saint Louis Park, MN, Daniel Anderson, UG1CA189863; Michigan Cancer Research Consortium NCORP, Ann Arbor, MI, Philip Stella, UG1CA189971; Montana Cancer Consortium NCORP, Billings, MT, Benjamin Marchello, UG1CA189872; Sanford NCI Community Oncology Research Program of the North Central Plains, Sioux Falls, SD, Preston Steen, UG1CA189825; Toledo Community Hospital Oncology Program CCOP, Toledo, OH, Rex Mowat; and Wichita NCI Community Oncology Research Program, Wichita, KS, Shaker Dakhil, UG1CA189808. Publisher Copyright: {\textcopyright} 2019, Springer Science+Business Media, LLC, part of Springer Nature.",
year = "2019",
month = jul,
day = "1",
doi = "10.1007/s11060-019-03194-z",
language = "English (US)",
volume = "143",
pages = "573--581",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "3",
}