Brain Tumor Clinical Trial
Official title:
St. Jude ELIOT: Phase 1 Evaluation of LY2606368, a Molecularly-Targeted CHK1/2 Inhibitor Therapy, in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group 4 or SHH Medulloblastoma Brain Tumors
Verified date | March 2024 |
Source | St. Jude Children's Research Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
SJELIOT is a phase 1 trial that aims to explore the combination of prexasertib with established DNA-damaging agents used in medulloblastoma to evaluate tolerance and pharmacokinetics in recurrent or refractory disease. Additionally, a small expansion cohort will be incorporated into the trial at the combination MTD/RP2D (maximum tolerated dose/recommended phase two dose) to detect a preliminary efficacy signal. Stratum A: Prexasertib and Cyclophosphamide Primary Objectives - To determine the safety and tolerability and estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of combination treatment with prexasertib and cyclophosphamide in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma and recurrent/refractory sonic hedgehog (SHH) medulloblastoma. - To characterize the pharmacokinetics of prexasertib in combination with cyclophosphamide. Secondary Objectives - To estimate the rate and duration of objective response and progression free survival (PFS) associated with prexasertib and cyclophosphamide treatment in this patient population. - To characterize the pharmacokinetics of cyclophosphamide and metabolites. Stratum B: Prexasertib and Gemcitabine Primary Objectives - To determine the safety and tolerability and estimate the MTD/RP2D of combination treatment with prexasertib and gemcitabine in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma. - To characterize the pharmacokinetics of prexasertib in combination with gemcitabine. Secondary Objectives - To estimate the rate and duration of objective response and PFS associated with prexasertib and gemcitabine treatment in this patient population. - To characterize the pharmacokinetics of gemcitabine and gemcitabine triphosphate (only at St. Jude Children's Research Hospital).
Status | Active, not recruiting |
Enrollment | 21 |
Est. completion date | October 2024 |
Est. primary completion date | May 1, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year to 24 Years |
Eligibility | Inclusion Criteria: Screening Phase - Participants with recurrent, refractory, or progressive medulloblastoma. - Age = 1 year and < 25 years at the time of screening. - Participants and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines. Exclusion Criteria: Screening Phase - Previous exposure to any CHK1 inhibitor. - Participants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities. - Participants with any history of QTc prolongation (i.e. QTc interval of > 480 msec). Inclusion Criteria: Strata A and B - Participant must be =1 year and <25 years of age at time of screening. - Participant must have recurrent, progressive or refractory Group 3/Group 4 or SHH medulloblastoma (per central pathology confirmation of primary tissue and/or relapsed tissue). Central pathology review previously completed at St. Jude Children's Research Hospital using equivalent methods can be used for enrollment. Note: Group 3/Group 4 may be referred to as Non-WNT Non-SHH (NWNS) in pathology reports. Medulloblastoma patients with indeterminate molecular subgroup after central pathology review are eligible for enrollment on stratum A. - Participant must have measurable or evaluable disease as defined in the protocol. - Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 3 weeks prior to study enrollment. - Participants must have had their last fraction of radiation (including CSI) at least 4 weeks prior to study enrollment. Participants who received radiation therapy for palliation must have had their last fraction of radiation at least 2 weeks prior to study enrollment. -- Note: Participants must have relapsed with recurrent, progressive or refractory disease after any prior radiation therapy that is not considered palliative. Palliative radiation therapy is defined as local small port RT to alleviate and/or palliate symptoms. (CSI, whole brain RT, large field/port RT, or large field/port multilevel spinal RT will not be considered palliative at any dose.) - Participant who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment with no plans for escalation. - Participant must have a Lansky (= 16 years) or Karnofsky (> 16 years) performance score of =50 and, in the opinion of the investigator, a minimum life expectancy of at least 6 weeks. -- Note: Participants 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. - Participant must have adequate bone marrow and organ function as defined as: - ANC = 1.0 x 10^9/L without growth factor support within 7 days - Platelet count = 75x 10^9/L without support of a platelet transfusion within 7 days - Hemoglobin =8.0 g/dL without support of a blood transfusion within 7 days - Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within institutional normal limits or corrected to within normal limits with supplements before first dose of study medication - Serum creatinine = the maximum serum creatinine based on age/gender: Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male, female); Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age := 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female). - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN. For the purposes of this study the ULN of ALT and AST is 45 U/L. - Total bilirubin = ULN; or if > ULN then direct bilirubin = 1.5 x ULN - Female participants of childbearing age must have a negative pregnancy test at the time of enrollment. - Participants of childbearing or child fathering potential must be willing to use medically acceptable form of birth control during treatment and for 16 weeks after stopping treatment. - Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines. Exclusion Criteria: Strata A and B - Participant who is receiving any other investigational agents. - Participants with other clinically significant medical disorders (i.e. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results. - Participant with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities as documented by a standard 12-lead ECG. - Shortening fraction of <27% by ECHO or ejection fraction of <50% by gated radionuclide study. - Prior history of QTc prolongation or QTc interval of > 480 msec. - Female participants who are breastfeeding a child. - Participants are excluded if unable to comply with guidelines listed in appendix I. |
Country | Name | City | State |
---|---|---|---|
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
Lead Sponsor | Collaborator |
---|---|
St. Jude Children's Research Hospital | Eli Lilly and Company |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum | The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days). | 1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment | |
Primary | To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine. | Incidence of adverse event data at least possibly related to treatment will be summarized in tables by treatment combination and by dose level. | Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment | |
Primary | To characterize the area under the concentration-time curve (AUC0-8) of prexasertib in combination with cyclophosphamide or gemcitabine. | Prexasertib area under the curve (AUC0-8) is estimated based on course 1, days 2 through 7 PK samples. | prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7 | |
Primary | To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine. | Prexasertib systemic clearance (CL) is estimated based on course 1, days 2 through 7 pharmacokinetic samples. | prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7 | |
Secondary | Rate of objective response (complete or partial response) by stratum | The incidence of objective responses (complete or partial response) observed during prexasertib and cyclophosphamide or gemcitabine treatment or during follow-up prior to progression or initiation of alternative cancer therapy. | Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment | |
Secondary | Duration of objective response by stratum | The duration of objective response is measured from the time the measurement criteria are met for complete response (CR) or partial response (PR), whichever is recorded first, until the first day on which recurrent or progressive disease is objectively documented. | Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment | |
Secondary | Progression-free survival for patients treated with prexasertib and cyclophosphamide or gemcitabine | Progression-free survival (PFS) is defined from the time of treatment initiation until disease progression or until death from any cause (whichever is earlier) for patients who experience an event and until the date of last follow-up for those who are alive and progression free at the time of analysis. PFS is estimated by Kaplan-Meier approach and median PFS is reported. | Up to 3 years from diagnosis | |
Secondary | To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide. | Cyclophosphamide area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2 PK samples. | prexasertib and cyclophosphamide treatment course 1, days 1 and 2 | |
Secondary | To characterize the systemic clearance (CL) of cyclophosphamide. | Cyclophosphamide systemic clearance (CL) is estimated based on course 1, days 1 and 2 PK samples. | prexasertib and cyclophosphamide treatment course 1, days 1 and 2 | |
Secondary | To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide. | 4-hydroxy-cyclophosphamide are under the curve AUC0-24h is estimated based on course 1, days 1 and 2 PK samples. | prexasertib and cyclophosphamide treatment course 1, days 1 and 2 | |
Secondary | To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide mustard. | Carboxyethylphosphoramide mustard area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2. PK samples. | prexasertib and cyclophosphamide treatment course 1, days 1 and 2 | |
Secondary | To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine. | Gemcitabine area under the curve (AUC0-4h) is estimated based on course 1, day 1 PK samples. | prexasertib and gemcitabine treatment course 1, day 1. | |
Secondary | To characterize the systemic clearance (CL) of gemcitabine. | Gemcitabine systemic clearance (CL) is estimated based on course 1, day 1 PK samples. | prexasertib and cyclophosphamide treatment course 1, day 1 | |
Secondary | To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine triphosphate (only at St. Jude Children's Research Hospital). | Gemcitabine triphosphate are under the curve AUC0-4h is estimated based on course 1, day 1 PK samples. | prexasertib and cyclophosphamide treatment course 1, day 1 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05023434 -
A Study to Measure the Effect of Brain Stimulation on Hand Strength and Function in Patients With Brain Tumors
|
||
Completed |
NCT04474678 -
Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!")
|
N/A | |
Completed |
NCT02768389 -
Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma
|
Early Phase 1 | |
Terminated |
NCT01902771 -
Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors
|
Phase 1 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT03286335 -
Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy
|
N/A | |
Recruiting |
NCT05968053 -
Detection of Microplastics and Nanoplastics in Neurosurgery Patients (DT-MiNi)
|
||
Recruiting |
NCT05358340 -
Dual Perfusion Imaging for Characterizing Vascular Architecture of Brain Lesions
|
N/A | |
Recruiting |
NCT03276676 -
[18F]Fluciclovine and [18F]FLT PET/CT Assessment of Primary High-Grade Brain Tumors
|
Phase 2 | |
Completed |
NCT02851355 -
Follow-up Survey of Patients Who Were Treated for Medulloblastoma or Primitive Neuroectodermal Tumors of the Central Nervous in Norway
|
||
Completed |
NCT02558569 -
The Use of Fentanyl in General Anesthesia for Craniotomy With or Without 0.5% Levobupivacaine Scalp Block
|
Phase 4 | |
Completed |
NCT02409121 -
A Novel Health Information Technology System (BMT Roadmap) for Pediatric BMT Patients and Caregivers
|
N/A | |
Completed |
NCT02713087 -
Vasopressor Effects in Anesthetized Patients
|
Phase 4 | |
Withdrawn |
NCT02165995 -
Use of Navigated Transcranial Magnetic Stimulation (nTMS) in Generated Motor and Language Mapping to Evaluate Brain Recovery Following Surgery
|
N/A | |
Terminated |
NCT02674945 -
Understanding and Improving Quality of Life Through a Wireless Activity Tracker: Observational Phase
|
||
Withdrawn |
NCT01202539 -
Real-time Assessment of Frameless Intrafraction Motion
|
||
Completed |
NCT01171469 -
Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
|
Phase 1 | |
Terminated |
NCT01044966 -
A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma
|
Phase 1/Phase 2 | |
Completed |
NCT00760409 -
Differentiating Recurrent Brain Tumor Versus Radiation Injury Using MRI
|
N/A | |
Completed |
NCT00503204 -
Phase I : Cediranib in Combination With Lomustine Chemotherapy in Recurrent Malignant Brain Tumour
|
Phase 1 |