MC230715 Pilot Study of the Mechanistic Feedback From CNS Tumors With Latent Residual Disease to Guide Individualized Therapies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Completion of 3 cycles
研究概览
简要总结
This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment Arm (Regimens 1-8):
- •Age ≥ 18 years
- •Prior diagnosis of a glioma treated with chemotherapy and/or radiation with stable disease based on Response Assessment in Neuro-Oncology (RANO) criteria
- •Must have IDH-mutant OR MGMT-methylated glioma
- •NOTE: Patients with any radiographic evidence of residual disease are eligible
- •Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2, and Karnofsky performance status >= 50
- •Hemoglobin ≥ 9.0 g/dL (≤ 15 days prior to registration)
- •Absolute neutrophil count (ANC) ≥ 1500/mm^3 (≤ 15 days prior to registration)
- •Platelet count ≥ 100,000/mm^3 (without transfusion ≤ 7 days preceding lab assessment) (≤ 15 days prior to registration)
- •Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN for patients with liver involvement) (≤ 15 days prior to registration)
- •Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (≤ 15 days prior to registration)
- •Average corrected QT interval (QTc) ≤ 450 ms on triplicate 12 lead electrocardiogram (ECG) ≤ 29 days prior to registration
- •NOTE: QTc intervals will be corrected using Fridericia's formula (Fridericia 1920)
- •Negative serum pregnancy test is required for persons of childbearing potential ≤ 8 days prior to registration
- •Presence of an implanted cranial CSF access device, such as Ommaya reservoir or ventriculoperitoneal shunt
- •Willingness to provide blood and CSF samples for research
- •Co-enrollment on the neuro-oncology biorepository [institutional review board (IRB) 12-003458] for collection of research blood and CSF samples
- •Provide written informed consent
- •Willingness to return to Mayo Clinic for follow-up
- •Inclusion Criteria - Monitoring Arm (Regimen 1 only):
- •Age ≥ 18 years
- •Prior diagnosis of a glioma
- •Negative serum pregnancy test is required for persons of childbearing potential ≤ 8 days prior to registration
- •Co-enrollment on the neuro-oncology biorepository [institutional review board (IRB) 12-003458] for collection of research blood and CSF samples
- •Provide written informed consent
- •Willingness to return to Mayo Clinic for follow-up
排除标准
- •Treatment Arm (Regimens 1-8):
- •Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
- •Patients who are not appropriate medical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings
- •Participants who are unable to swallow tablets or who are at risk for impaired absorption of oral medication
- •NOTE: This includes but not limited to, refractory vomiting, gastric resection/bypass, or duodenal/jejunal resection
- •NOTE: An exception can be granted for such patients if no oral medications are planned (i.e., patient will receive only IV or intradermal agents)
- •Patients with known hypersensitivity or allergy to all of the study drugs on the protocol (known hypersensitivity or allergy to one drug does not preclude participation in this protocol)
- •Inability to undergo MRI scans
- •NOTE: These patients may be enrolled in the Monitoring Arm
- •Exclusion Criteria - Monitoring Arm (Regimen 1 only):
- •Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
- •Current or past medical history or uncontrolled concurrent illness which limits safety or compliance with study proceedings
- •Known hypersensitivity or allergy to radioactive tracers
- •Inability to undergo clinical imaging
研究组 & 干预措施
Regimen 2 (dasatinib, quercetin)
Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Dasatinib (Drug)
Regimen 4 (temozolomide)
Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Regimen 4 (temozolomide)
Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Temozolomide (Drug)
Regimen 6 (fisetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 2 (dasatinib, quercetin)
Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Regimen 3 (fisetin)
Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Monitoring Arm
Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Monitoring Arm
Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 2 (dasatinib, quercetin)
Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Regimen 2 (dasatinib, quercetin)
Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 3 (fisetin)
Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Regimen 3 (fisetin)
Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 4 (temozolomide)
Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Regimen 4 (temozolomide)
Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Positron Emission Tomography (Procedure)
Regimen 6 (fisetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Biospecimen Collection (Procedure)
Regimen 6 (fisetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Monitoring Arm
Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Monitoring Arm
Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Patient Observation (Other)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Quercetin (Drug)
Regimen 6 (fisetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Temozolomide (Drug)
Regimen 2 (dasatinib, quercetin)
Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Quercetin (Drug)
Regimen 3 (fisetin)
Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Fisetin (Drug)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Temozolomide (Drug)
Regimen 5 (dasatinib, quercetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Dasatinib (Drug)
Regimen 6 (fisetin, temozolomide)
Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
干预措施: Fisetin (Drug)
结局指标
主要结局
Completion of 3 cycles
时间窗: Up to 16 weeks
Will evaluate feasibility of serially screening multiple candidate therapies or combinations based on individualized empiric biological feedback from biospecimens and imaging. This will be measured as the percentage of patients successfully completing 3 cycles of drug administration (study visits). A cycle is 35 +/- 7 days. Regimen will be considered feasible if at least 2/3 of patients can achieve this target.
Turnaround time for scan and marker data
时间窗: Up to 16 weeks (completion of 3 cycles)
Will also evaluate feasibility as the turnaround time for scan and marker data that is used to determine if patients should stay on current therapy or move to the next regimen. The outcomes will be cycle-specific. A cycle is 35 +/- 7 days. The target for this is a mean turnaround time of 3 days; if the maximum turnaround time exceeds 5 days, this will prompt an evaluation of process to identify barriers.
次要结局
- Incidence of adverse events(Up to 3 years)
- Change in senescence-associated proteins(Baseline; up to 3 years)
- Cell-free mitochondrial deoxyribonucleic acid (DNA)(Baseline; up to 3 years)
- 2-Hydroxyglutarate (2-HG)(Baseline; up to 3 years)
- Amplified DNA junctions(Baseline; up to 3 years)
- Volume of disease(Baseline; up to 3 years)