Phase 1
Completed N=30
Prexasertib in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors
Childhood Solid Neoplasm · Recurrent Malignant Solid Neoplasm · Recurrent Primary Central Nervous System Neoplasm · Refractory Malignant Solid Neoplasm
Source: ClinicalTrials.gov NCT02808650 ↗
Enrolled (actual)
30
Serious AEs
50.0%
Results posted
Dec 2023
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Prexasertib — 150 mg/m^2
Summary
This phase I trial studies the side effects and best dose of prexasertib in treating pediatric patients with solid tumors that have come back after a period of time during which the tumor could not be detected or does not respond to treatment. Checkpoint kinase 1 inhibitor LY2606368 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Prexasertib |
150 | — |
| PRIMARY Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib |
0; 0; 0; 0; 0 | — |
| PRIMARY Area Under the Concentration Time Curve for Prexasertib |
1718.7; 2285.5; 2534.4; 4206.6; 3097.7 | — |
| SECONDARY Antitumor Activity of Prexasertib |
0; 0; 0; 0; 0 | — |
| SECONDARY CHK1/2 Expression Status |
2; 0; 1; 0; 1; 0 | — |
| SECONDARY TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY Autophosphorylation of CHK1 and H2AX |
— | — |
Eligibility Criteria
Inclusion Criteria
- Patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or in patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 % for patients = = 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days must have elapsed from last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
- Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade = = 14 days must have elapsed since last dose of corticosteroid
- Hematopoietic growth factors: >= 14 days must have elapsed since the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
- Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days must have elapsed since the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
- Stem cell infusions (with or without total body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days must have elapsed after infusion, and no evidence of graft-versus-host disease (GVHD)
- Autologous stem cell infusion including boost infusion: >= 42 days must have elapsed after completion
- Cellular therapy: >= 42 days must have elapsed since the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- X ray (XRT)/external beam irradiation including protons: >= 14 days must have elapsed after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine metaiodobenzylguanidine [131I-MIBG]): >= 42 days must have elapsed since systemically administered radiopharmaceutical therapy
- Patients must not have received prior exposure to LY2606368
- For patients with solid tumors without known bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 75, 000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin >= 8.0 g/dl at baseline (may receive packed red blood cell [PRBC] transfusions)
- Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalatio
Data sourced from ClinicalTrials.gov (NCT02808650). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.