Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Study Design
2.2. Study Population
2.3. Treatment Plan
2.4. Objectives and Assessments
2.5. Statistics
2.6. Molecular Biomarker Analysis
3. Results
3.1. Dose-Escalation Phase
3.2. Dose-Expansion Phase
3.3. Efficacy
3.4. Molecular Biomarkers and Correlation with Efficacy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient Quantitative Characteristics | Median (Range) | |
---|---|---|
Age (years) | 51.4 (33.3–76.5) | |
KPS (%) | 90 (70–100) | |
Barthel (%) | 100 (75–100) | |
Mini-mental | 29 (20–30) | |
Time from surgery to study treatment (weeks) | 5.4 (4–8) | |
Patient Qualitative Characteristics | n (%) | |
Gender | Male | 16 (44.4) |
Female | 20 (55.6) | |
Histological diagnosis | Glioblastoma | 34 (94.4) |
Astrocytoma | 1 (2.8) | |
NE | 1 (2.8) | |
MGMT methylation | Yes | 16 (44.4) |
No | 12(33.3) | |
NE/UK | 8 (22.2) | |
IDH1/2 mutations | Yes | 3 (8.3) |
No | 29 (80.6) | |
NE/UK | 4 (11.1) | |
EGFR amplification | Yes | 12 (33.3) |
No | 14 (38.9) | |
NE/UK | 10 (27.8) | |
ALK alterations | Yes | 0 (0) |
No | 26 (72.2) | |
NE/UK | 10 (27.8) | |
MET alterations | Yes | 1 (2.8) |
No | 25 (69.4) | |
NE/UK | 10 (27.8) | |
ROS alterations | Yes | 0 (0) |
No | 26 (72.2) | |
NE/UK | 10 (27.8) |
Phase | Dose Escalation Phase | ||||
---|---|---|---|---|---|
Crizotinib dose | 200 mg/QD | 250 mg/QD | 200 mg/BID | 250 mg/QD | Any |
Grade | Grade ≥3 | Grade ≥3 | Grade ≥3 | Grade ≥3 | Grade ≥3 |
Number of patients n (%) | 3 (100%) | 6 (100%) | 3 (100%) | 25 (100%) | 37 (100%) |
Fatigue | 1 (33.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (2.7) |
Transaminitis | 1 (33.3) | 1 (16.7) * | 1 (33.3) * | 5 (20.0) | 8 (21.6) |
Neutrophil count decreased | 2 (66.7) | 2 (33.3) | 1 (33.3) * | 1 (4.0) | 6 (16.2) |
Platelet count decreased | 1 (33.3) | 1 (16.7) | 0 (0.0) | 2 (8.0) | 4 (10.8) |
Constipation | 0 (0.0) | 0 (0.0) | 1 (33.3) * | 0 (0.0) | 1 (2.7) |
Lymphocyte count decreased | 1 (33.3) | 0 (0.0) | 0 (0.0) | 1 (4.0) | 2 (5.4) |
White blood cell decreased | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (4.0) | 1 (2.7) |
Alanine aminotransferase increased | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (8.0) | 2 (5.4) |
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Martínez-García, M.; Velasco, G.; Pineda, E.; Gil-Gil, M.; Alameda, F.; Capellades, J.; Martín-Soberón, M.C.; López-Valero, I.; Tovar Ambel, E.; Foro, P.; et al. Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial. Cancers 2022, 14, 2393. https://doi.org/10.3390/cancers14102393
Martínez-García M, Velasco G, Pineda E, Gil-Gil M, Alameda F, Capellades J, Martín-Soberón MC, López-Valero I, Tovar Ambel E, Foro P, et al. Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial. Cancers. 2022; 14(10):2393. https://doi.org/10.3390/cancers14102393
Chicago/Turabian StyleMartínez-García, María, Guillermo Velasco, Estela Pineda, Miguel Gil-Gil, Francesc Alameda, Jaume Capellades, Mari Cruz Martín-Soberón, Israel López-Valero, Elena Tovar Ambel, Palmira Foro, and et al. 2022. "Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial" Cancers 14, no. 10: 2393. https://doi.org/10.3390/cancers14102393