NCT04900792进行中（未招募）1 期
A First-in-Human Clinical Trial of Pharmacologic Ascorbate and Ferumoxytol Combined With Concomitant Temozolomide and External Beam Radiation Therapy for Newly Diagnosed Glioblastoma
Bryan Allen2 个研究点 分布在 1 个国家目标入组 16 人开始时间: 2023年2月28日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Determination of recommended phase 2 ferumoxytol dosing regimen
研究概览
简要总结
This clinical trial evaluates adding ferumoxytol and pharamcologic ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive ferumoxytol and pharmacologic ascorbate in addition to the standard treatment.
详细描述
The initial, standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth).
Participants in this trial will:
- receive intravenous (IV) ferumoxytol the day before starting radiation, then around radiation treatments 6, 25, and 31.
- receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase.
- provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
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
- •Willingness and ability to provide informed consent consistent with Good Clinical Practice (i.e., legally authorized representative will not be used / allowed for this study).
- •Stated willingness to comply with all study procedures for the duration of the study
- •Aged 18 years or older.
- •Newly diagnosed (i.e., within 6 weeks), histologically or molecularly confirmed glioblastoma or diffuse midline glioma.
- •Therapy to begin within 6 weeks of last surgery
- •Able to take oral medication
- •ECOG performance status of 0, 1, or 2 (KPS of >50)
- •Recommended to receive temozolomide and radiation therapy
- •Medically fit, as determined by the prescribing oncologists, to undergo temozolomide and radiation therapy.
- •Agree to use of highly effective contraception from screening until at least 90 days after the last study treatment (study participant should not discontinue contraception until discussing with their treating oncologist(s)).
- •Not have significant co-morbid central nervous system disease, such as multiple sclerosis.
- •Agree to Lifestyle Considerations throughout study duration
排除标准
- •Current use of the following drugs and cannot have a drug substitution or decline the drug substitution: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide. Pharmacologic ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
- •Current use of antiretroviral drugs (e.g., nelfinavir, abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine). Pharmacologic ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.
- •Insulin requirement
- •Requires blood glucose monitoring using finger-stick glucose checks.
- •Medical requirement or indication for iron supplementation (including ferumoxytol, ferrous gluconate, ferrous fumarate, or ferrous sulfate). NOTE: Over the counter, patient-elective supplementation is acceptable.
- •Inability to undergo MR imaging.
- •Pregnancy or lactation (note: potential participants should not engage in 'pump & dump' strategy; lactation must be discontinued).
- •Known allergic reactions to ferumoxytol.
- •History of Steven's Johnson Syndrome
- •History of hemochromatosis.
- •Prior radiation treatment that would result in field overlap. For potential participants who have undergone nuclear medicine therapy, including PRRT, the study's radiation oncologist must approve study entry.
- •G6PD (glucose-6-phosphate dehydrogenase) deficiency
- •Platelet count < 100,000 /mm3 within 21 days of first treatment
- •Creatinine ≥ 1.5x the institutional upper limit of normal within 21 days of the first treatment or if creatinine is elevated a creatinine clearance of < 60 mL/(min 1.73 m2)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring inpatient admission or a delay to start of therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Treatment with another investigational drug within 30 days prior to study treatment day
- •Imaging trials (including investigational PET or NM tracers) as well as observational trials are acceptable.
- •Clinical trials with an endpoint of treating the patient's cancer, including behavioral, nutritional and/or device human subject studies.
研究组 & 干预措施
Cohort 2
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of
干预措施: External beam radiation therapy (Radiation)
Cohort 1 (starting)
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.
干预措施: Ferumoxytol injection (Drug)
Cohort 1 (starting)
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.
干预措施: External beam radiation therapy (Radiation)
Cohort 1 (starting)
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.
干预措施: Pharmacological ascorbate (Drug)
Cohort 2
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of
干预措施: Ferumoxytol injection (Drug)
Cohort 2
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of
干预措施: Pharmacological ascorbate (Drug)
Cohort 1 (starting)
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.
干预措施: Temozolomide (Drug)
Cohort 2
Experimental
Radiation Phase
- Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
- Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
- Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
- Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).
Adjuvant Phase
- Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
- Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
- Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of
干预措施: Temozolomide (Drug)
结局指标
主要结局
Determination of recommended phase 2 ferumoxytol dosing regimen
时间窗: From treatment day 1 through 12 weeks after completing radiation
The recommended dose will be determined by incidence of dose limiting toxicities.
Number of Ferumoxytol-related Dose Limiting Toxicities (DLTs)
时间窗: From treatment day 1 through 12 weeks after completing radiation
The recommended dose will be determined by incidence of dose limiting toxicities.
次要结局
- Estimate progression free survival (PFS)(From treatment day 1 to disease progression, up to 60 months post-treatment)
- Tumor size(Baseline and 12 weeks post-radiation)
- Clinical response(12 weeks post-radiation)
- Estimate overall survival (OS)(Time (measured in days) until death from any cause, up to 20 years post-treatment)
- Estimate Objective Response Rate (ORR)(12 weeks post-radiation)
- Number of Treatment-Related Adverse Events(Up to 36 months post-radiation)
- Estimate Progression Free Survival (PFS)(From treatment day 1 to disease progression, up to 16 months post-treatment)
- Estimate Overall Survival (OS)(Time (measured in months) until death from any cause, up to 26 months post-treatment)
- Disease Response(12 weeks post-radiation)
- Number of Participants With Treatment-Related Adverse Events(Up to 36 months post-radiation)
研究者
Bryan Allen
Associate Professor
University of Iowa
研究点 (2)
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