Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of grade 3, 4, & 5 adverse events during radiation
研究概览
简要总结
This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for treatment of pancreatic cancer.
详细描述
This phase 1 study will test the safety of adding high dose ascorbate (vitamin C) to standard chemoradiation. The ascorbate is infused during external beam radiation therapy treatment.
For patients eligible for this trial, standard treatment for their cancer includes radiation therapy combined with weekly gemcitabine (a chemotherapy).
Participants will:
- receive high doses of intravenous (IV) ascorbate during their daily radiation therapy treatments. Radiation treatments are given once a day, Monday through Friday.
- have routine doctor's visits and be asked about any side effects they are experiencing.
This is a phase 1 study that will evaluate the side effects of adding ascorbate to standard therapy. The dose given to a participant will be determined by how well other participants have tolerated ascorbate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Patients must have histologically or cytologically diagnosed pancreatic adenocarcinoma. Documentation of disease extent by CT scan is required. Radiologically measurable disease is not required.
- •Age ≥ 18 years
- •ECOG performance status 0, 1, or 2 (Karnofsky > 50%).
- •A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below:
- •Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
- •Platelets ≥ 100,000 per mm3
- •Leukocytes ≥ 3,000 per mm3
- •Serum blood chemistries within 21 days of radiation fraction 1, as defined below:
- •Creatinine ≤ 1.5 x UIHC upper limit of normal or creatinine clearance of at least 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal.
- •Total bilirubin ≤ 2 x UIHC upper limit of normal
- •ALT ≤ 2.5 times the UIHC upper limit of normal
- •AST ≤ 2.5 times the UIHC upper limit of normal
- •PT/INR within normal limits (UIHC)
- •Tolerate one test dose (15g) of ascorbate.
- •Not pregnant.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •G6PD (glucose-6-phosphate dehydrogenase) deficiency.
- •Prior abdominal radiotherapy that would result in overlap of fields. The treating radiation oncologist should review prior RT fields as available.
- •Adjuvant therapy (including radiation therapy) within 2 calendar weeks. Toxicities from prior therapy for the malignancy should resolve to grade 1 or less.
- •Patients actively receiving insulin are excluded.
- •Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs.
- •Second malignancy other than non-melanoma skin cancers within the past 5 years.
- •Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable).
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
- •Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are well documented.
- •Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 1 study.
研究组 & 干预措施
50g Ascorbate
This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Ascorbate (Drug)
50g Ascorbate
This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Gemcitabine (Drug)
50g Ascorbate
This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Radiation therapy (Radiation)
75g Ascorbate
If the 50g arm is tolerated, the study opens the 75g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Ascorbate (Drug)
75g Ascorbate
If the 50g arm is tolerated, the study opens the 75g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Gemcitabine (Drug)
75g Ascorbate
If the 50g arm is tolerated, the study opens the 75g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Radiation therapy (Radiation)
100g Ascorbate
If the 75g arm is tolerated, the study opens the 100g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Ascorbate (Drug)
100g Ascorbate
If the 75g arm is tolerated, the study opens the 100g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Gemcitabine (Drug)
100g Ascorbate
If the 75g arm is tolerated, the study opens the 100g arm.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Radiation therapy (Radiation)
25g Ascorbate
This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Ascorbate (Drug)
25g Ascorbate
This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Gemcitabine (Drug)
25g Ascorbate
This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened.
- Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
- Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
- Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
Number of grade 3, 4, & 5 adverse events during radiation
时间窗: Weekly during therapy for up to 10 weeks
Assess grade 3 and higher adverse events. Evaluate the frequency and severity against the published literature to determine the likely causality between ascorbate and the adverse event(s).
次要结局
- Time to progression(Monthly, up to 10 years post-treatment)
- Number of grade 3, 4, & 5 adverse events post-treatment(every 3 months for 2 years)
- Overall survival(Monthly, up to 10 years post-treatment)
研究者
Joseph J. Cullen
Professor
University of Iowa