Citations 3
CODEL (Alliance-N0577; EORTC-26081/22086; NRG-1071; NCIC-CEC-2): Phase III Randomized Study of RT vs. RT+TMZ vs. TMZ for Newly Diagnosed 1p/19q-Codeleted Anaplastic Oligodendroglial Tumors. Analysis of Patients Treated on the Original Protocol Design (PL02
Jaeckle, Kurt A. , Vogelbaum, Michael A. , Anderson, S. Keith , Aldape, Kenneth , Cerhan, Jane H. , Nordstrom, Donald G., Jenkins, Robert B. , Raizer, Jeffrey J. , Flynn, Patrick , Dhermain, F., Cairncross, J. G., Brown, Paul D. , Ballman, Karla V. , Giannini, Caterina , Wefel, Jeffrey S. , Klein, Martin , Bent, Martin J. van den , Wick, Wolfgang , Flynn, Patrick, Galanis, Evanthia
Neurology | December 7, 2023 | Volume: 86 | Issue: 16_supplement | Pages: No page available
CTNI-29. CODEL: PHASE III TRIAL OF RT ALONE, RT PLUS TMZ, OR TMZ ALONE FOR NEWLY-DIAGNOSED, 1p/19q CODELETED ANAPLASTIC OLIGODENDROGLIOMA. ANALYSIS FROM THE INITIAL STUDY DESIGN. (NCCTG N0577, ALLIANCE)
Jaeckle, Kurt A. , Brown, Paul D. , Jenkins, Robert B. , Cairncross, Gregory, Aldape, Kenneth, Anderson, S. Keith , Schiff, David , Raizer, Jeffrey J. , Dhermain, F., Nordstrom, Donald G., Flynn, Patrick J. , Vogelbaum, Michael A. , Ballman, Karla V. , Bent, Martin J. van den , Giannini, Caterina , Galanis, Evanthia , Wick, Wolfgang , Weller, Michael , Dixon, Jesse G. , Cerhan, James R. , Wefel, Jeffrey S. , Klein, Martin , Grossman, Stuart A.
Neuro-Oncology | December 4, 2020 | Volume: 22 | Issue: Supplement_2 | Pages: ii48-ii49
Abstract BACKGROUND The original 3-arm CODEL design included a radiotherapy (RT)-alone control arm, an RT plus temozolomide (TMZ) arm, and an exploratory TMZ-alone arm. We report the analysis involving patients treated per the initial design. METHODS Adults (18+ years) with newly-diagnosed 1p/19q codeleted WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant TMZ (Arm B); or TMZ alone (Arm C). Primary endpoint was OS, Arm A vs. B. Secondary comparisons were performed for OS and PFS, comparing pooled RT arms with the TMZ-alone arm. RESULTS 36 patients were randomized equally to the three arms. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients had progressed, versus 37.5% (9/24) patients on the RT arms. PFS was shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) of RT-treated patients. OS did not statistically differ between arms, although this comparison was underpowered. After adjustment for IDH status (mutated vs. wildtype) in a Cox regression model, with IDH status and RT treatment status as co-variables (Arm C vs pooled A and B), PFS remained shorter for patients not receiving RT (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), and OS differences remained non-significant ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% patients (Arms A, B and C, respectively). Neurocognitive assessments, comparing baseline and 3 month timepoints, showed no significant differences between arms. CONCLUSIONS TMZ-alone treated patients experienced significantly shorter PFS than patients treated on the pooled RT arms, which remained significant when adjusting for IDH status. CODEL has been redesigned to compare the efficacy and toxicity of RT+PCV versus RT+TMZ. Clinicaltrials.gov Identifier: NCT00887146. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org.
CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design
Jaeckle, Kurt A. , Ballman, Karla V. , Bent, Martin J. van den , Giannini, Caterina , Galanis, Evanthia , Brown, Paul D. , Jenkins, Robert B. , Cairncross, J. Gregory , Wick, Wolfgang , Weller, Michael , Aldape, Kenneth , Anderson, S. Keith , Cerhan, Jane H. , Klein, Martin , Schiff, David , Raizer, Jeffrey J. , Dhermain, F., Nordstrom, Donald G., Flynn, Patrick J. , Vogelbaum, Michael A. , Dixon, Jesse G. , Weller, Michael , van den Bent, Martin J , Galanis, Evanthia , Giannini, Caterina , Wick, Wolfgang , Jaeckle, Kurt A , Ballman, Karla , Dixon, Jesse G , Dixon, Jesse G , Wefel, Jeffrey S. , Grossman, Stuart A.
Neuro-Oncology | July 13, 2020 | Volume: 23 | Issue: 3 | Pages: 457-467
Abstract Background We report the analysis involving patients treated on the initial CODEL design. Methods Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. Results Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. Conclusions TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.