Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Eligibility
2.2. Drug Administration
2.3. Study Evaluations
2.4. Pharmacokinetics
3. Results
3.1. Patient Characteristics
3.2. Toxicities
3.3. PK Studies
3.4. Response Evaluation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Value |
---|---|
Age, years | |
Median | 12 |
Range | 3–20 |
Sex | |
Male | 13 |
Female | 12 |
Diagnosis | |
Sarcoma | |
Osteosarcoma | 8 |
Rhabdomyosarcoma | 4 |
Ewing Sarcoma/PNET | 4 |
Synovial sarcoma | 1 |
Neuroblastoma | 7 |
Brain Tumor | |
Ependymoma | 2 |
High-grade glioma | 1 |
Medulloblastoma | 1 |
Adrenocortical carcinoma | 1 |
Wilms Tumor | 1 |
Prior chemotherapy regimens, number | |
Median | 1.5 |
Range | 0–10 |
Prior radiation therapy | 22 |
Dose Level | Topotecan Dose (mg/m2/Day) | Pazopanib Dose (mg/m2/Day) | Patients Entered | Patients Evaluable | Patients with DLT |
---|---|---|---|---|---|
0 | 0.12 | 125 | 6 | 5 | 0 |
1 | 0.16 | 125 | 6 | 5 | 0 |
2 | 0.22 | 125 | 7 | 5 | 0 |
3 | 0.22 | 160 | 6 | 6 | 0 |
4 | 0.3 | 160 | 5 | 5 | 2 * |
Number of Patients | ||||
---|---|---|---|---|
Maximum Grade Observed per Patient during Cycle 1 (n = 28) | Maximum Grade Observed per Patient across All Cycles (n = 28) | |||
Toxicity Type | Any Grade | Grade 3/4 | Any Grade | Grade 3/4 |
Hematologic | ||||
Thrombocytopenia | 12 | 3 | 14 | 4 * |
Neutropenia | 15 | 5 | 19 | 9 |
Lymphopenia | 13 | 3 | 20 | 4 |
Anemia | 16 | 2 | 20 | 5 |
Non-hematologic † | ||||
GI/metabolic | ||||
Constipation | 7 | 0 | 10 | 0 |
Diarrhea | 3 | 0 | 8 | 1 |
Nausea | 11 | 0 | 14 | 0 |
Vomiting | 9 | 0 | 13 | 0 |
Anorexia | 8 | 0 | 15 | 0 |
ALT elevation | 12 | 2 | 14 | 2 * |
AST elevation | 13 | 2 | 18 | 3 |
Bilirubin elevation | 5 | 0 | 8 | 0 |
Hypoalbuminemia | 6 | 0 | 10 | 1 |
Lipase elevation | 4 | 2 | 7 | 3 |
Creatinine elevation | 3 | 0 | 4 | 0 |
Hypocalcemia | 4 | 0 | 12 | 1 |
Hyperkalemia | 3 | 0 | 9 | 0 |
Hypokalemia | 3 | 0 | 3 | 0 |
Hypomagnesemia | 4 | 0 | 7 | 0 |
Hypophosphatemia | 5 | 0 | 8 | 0 |
Cardiac/respiratory | ||||
Sinus tachycardia | 3 | 0 | 4 | 0 |
Cough | 5 | 0 | 9 | 0 |
Nervous system | ||||
Ataxia | 3 | 0 | 3 | 0 |
Headache | 4 | 0 | 6 | 1 |
Psychiatric | ||||
Anxiety | 3 | 0 | 5 | 0 |
Insomnia | 3 | 0 | 5 | 0 |
Musculoskeletal/constitutional | ||||
Fatigue | 11 | 0 | 17 | 0 |
Pain | 6 | 0 | 13 | 1 |
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Manji, A.; Samson, Y.; Deyell, R.J.; Johnston, D.L.; Lewis, V.A.; Zorzi, A.P.; Berman, J.N.; Brodeur-Robb, K.; Morrison, E.; Kee, L.; et al. Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial. Cancers 2022, 14, 2985. https://doi.org/10.3390/cancers14122985
Manji A, Samson Y, Deyell RJ, Johnston DL, Lewis VA, Zorzi AP, Berman JN, Brodeur-Robb K, Morrison E, Kee L, et al. Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial. Cancers. 2022; 14(12):2985. https://doi.org/10.3390/cancers14122985
Chicago/Turabian StyleManji, Arif, Yvan Samson, Rebecca J. Deyell, Donna L. Johnston, Victor A. Lewis, Alexandra P. Zorzi, Jason N. Berman, Kathy Brodeur-Robb, Ellen Morrison, Lynn Kee, and et al. 2022. "Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial" Cancers 14, no. 12: 2985. https://doi.org/10.3390/cancers14122985