Prexasertib in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors
NCT ID: NCT02808650
Last Updated: 2023-12-20
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
30 participants
INTERVENTIONAL
2017-02-27
2021-03-31
Brief Summary
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Detailed Description
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I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of prexasertib (LY2606368) administered as an intravenous (IV) infusion over 60 minutes, every 14 days of a 28-day cycle to children with recurrent or refractory solid tumors.
II. To define and describe the toxicities of LY2606368 administered on this schedule.
III. To characterize the pharmacokinetics of LY2606368 in children with recurrent or refractory cancer.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of LY2606368 within the confines of a phase 1 study.
II. To examine checkpoint kinase (CHK)1/2 expression status in archival tumor tissue from solid tumor pediatric patients using immunohistochemistry.
III. To evaluate tumor tissue for deletion and/or mutation of tumor protein 53 (TP53) as a potential biomarker of Chk1 inhibition.
IV. To evaluate autophosphorylation of Chk1 and H2A histone family, member x (H2AX) in peripheral blood mononuclear cells as a potential pharmacodynamic marker of LY2606368 activity.
OUTLINE: This is a dose-escalation study.
Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (prexasertib)
Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis
Correlative studies
Pharmacokinetic (PK) study
Correlative studies
Prexasertib
Given IV
Interventions
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Laboratory Biomarker Analysis
Correlative studies
Pharmacokinetic (PK) study
Correlative studies
Prexasertib
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 =\< 16 years of age
* Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
* \>= 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 =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 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-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* Age: maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male and female)
* 2 to \< 6 years: 0.8 (male and female)
* 6 to \< 10 years: 1 (male and female)
* 10 to \< 13 years: 1.2 (male and female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by gated radionuclide study
* Corrected QT (QTc) =\< 480 msec
* Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; If possible, alternative agents should be considered
* Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4) resulting from prior therapy must be =\< grade 2
* For patients with CNS tumors, any baseline neurologic deficit, including seizures, must be stable for at least one week prior to initiating study treatment
* All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
* Tissue blocks or slides must be sent if available; if tissue blocks or slides are unavailable, the study chair must be notified prior to study enrollment
Exclusion Criteria
* Corticosteroids: Patients receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Strong CYP1A2 inhibitors: Patients must not have received strong CYP1A2 inhibitors (ciprofloxacin, fluvoxamine, zafirlukast) for at least 7 days prior to enrollment and must not receive them for the duration of the study
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to LY2606368 or to its formulation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
12 Months
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Cynthia J Wetmore
Role: PRINCIPAL_INVESTIGATOR
COG Phase I Consortium
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Seattle Children's Hospital
Seattle, Washington, United States
Countries
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References
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Cash T, Fox E, Liu X, Minard CG, Reid JM, Scheck AC, Weigel BJ, Wetmore C. A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515). Pediatr Blood Cancer. 2021 Sep;68(9):e29065. doi: 10.1002/pbc.29065. Epub 2021 Apr 21.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2016-00643
Identifier Type: REGISTRY
Identifier Source: secondary_id
ADVL1515
Identifier Type: -
Identifier Source: secondary_id
ADVL1515
Identifier Type: OTHER
Identifier Source: secondary_id
ADVL1515
Identifier Type: OTHER
Identifier Source: secondary_id
ADVL1515
Identifier Type: -
Identifier Source: org_study_id