NCT03883919已完成1 期
A Pilot Study of Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities
研究概览
简要总结
Given the efficacy of nanoliposomal irinotecan as a second-line regimen in pancreatic ductal adenocarcinoma (PDAC), together with the favorable toxicity profile of paricalcitol and its interplay with irinotecan metabolism, the investigators propose a second-line pilot study in advanced PDAC that will enroll patients who have progressed on a gemcitabine-based regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed pancreatic adenocarcinoma.
- •Must have progressed on or become intolerant to gemcitabine-containing therapy in the advanced setting (not resectable). This is intended to be a second-line trial.
- •Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- •At least 18 years of age.
- •Life expectancy > 3 months.
- •ECOG performance status ≤ 1
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ 1.5 x ULN
- •Serum albumin > 3g/dL
- •AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless there are liver metastases, in which case AST and ALT ≤ 5.0 x IULN
- •Creatinine ≤ 1.5 x IULN OR GFR > 50 mL/min
- •Corrected calcium < 10.3 mg/dL
- •Phosphorus ≤ 4.5 mg/dL
- •Patients will require a 2-week washout period from previous gemcitabine-based systemic therapy, a 2-week washout period from previous radiation therapy, and a 4-week washout period from major surgery prior to the first planned dose of study treatment.
- •Prior clinically significant treatment-related toxicity must recover to grade 1 or less prior to the first planned dose of study treatment.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •More than one prior systemic treatment in the advanced setting. Disease recurrence within 6 months of adjuvant therapy is considered one line of systemic treatment.
- •Patients with active renal, ureteral, or bladder stones on the screening imaging.
- •Current use of or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
- •A history of other malignancy within 2 years previous, with the exception of those basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix.
- •Currently receiving any other investigational agents.
- •Patients who received FOLFIRINOX or FOLFIRI in the neoadjuvant or adjuvant setting who experienced disease recurrence within 6 months will be excluded (patients who received 5-FU or capecitabine as a radiosensitizer are permitted to enroll.)
- •Patients with known active/ progressive brain metastases or leptomeningeal involvement will be excluded due to their poor prognosis. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents used in the study.
- •Clinically significant ascites that requires therapeutic paracentesis or significant pleural effusion that requires therapeutic thoracentesis.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
- •Known HIV-positivity not on anti-retroviral therapy, or with CD4+ T cell count < 200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell count > 200/ul will be included).
研究组 & 干预措施
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: 5-FU (Drug)
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Leucovorin (Drug)
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Liposomal Irinotecan (Drug)
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Paricalcitol (Drug)
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Serum and plasma blood samples (Procedure)
Group 1: Paricalcitol 75 mcg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 75 mcg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Tumor biopsy (Procedure)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: 5-FU (Drug)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Leucovorin (Drug)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Liposomal Irinotecan (Drug)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Paricalcitol (Drug)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Serum and plasma blood samples (Procedure)
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
Experimental
- 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
- Paricalcitol 7 mcg/kg on Days 1 and 8
- Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
干预措施: Tumor biopsy (Procedure)
结局指标
主要结局
Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities
时间窗: Through 30 days after completion of paricalcitol treatment (estimated to be 28 weeks)
-Toxicity will be graded using CTCAE version 5.0
次要结局
- Duration of overall response(Through completion of treatment (estimated to be 20 weeks))
- Overall response rate (ORR)(Through completion of treatment (estimated to be 20 weeks))
- Progression-free survival (PFS)(Through completion of follow-up (estimated to be 72 weeks))
- Overall survival (OS)(Through completion of follow-up (estimated to be 72 weeks))
- CA19-9 biochemical response rate(Through beginning of cycle 10 (estimated to be 18 weeks))
- Duration of stable disease(Through completion of treatment (estimated to be 20 weeks))
- Duration of complete response(Through completion of treatment (estimated to be 20 weeks))
研究者
研究点 (1)
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