A Phase 1 Study of Gemcitabine, Nab-Paclitaxel, and Bosentan in Patients With Unresectable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial studies the side effects and best dose of bosentan and how well it works when given together with gemcitabine and nab-paclitaxel for the treatment of pancreatic cancer that cannot be removed by surgery (unresectable). Bosentan may block the hormone endothelin and prevent the growth and spread of pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bosentan with chemotherapy (gemcitabine and nab-paclitaxel) may work better in treating patients with pancreatic cancer compared to chemotherapy alone.
详细描述
PRIMARY OBJECTIVE:
I. To assess the safety, toxicity and feasibility of administering bosentan with nab-paclitaxel and gemcitabine.
SECONDARY OBJECTIVES:
I. To assess the response rate associated with this combination therapy in first line pancreatic cancer patients.
II. To assess the progression-free survival and overall survival of all patients who start protocol therapy, and describe the outcomes based on measures of compliance during the lead-in week, and compliance with supplement during chemotherapy.
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
- •Main Inclusion Criteria
- •Adult patients with unresectable pancreatic carcinoma
- •Patients must be a candidate to receive one of the following chemotherapy combinations as determined by the treating physician:
- •Arm A2: gemcitabine plus nab-paclitaxel given every 2 weeks (arm A1 is closed per this amendment)
- •Arm B: mFOLFIRINOX given every 2 weeks
- •Willingness to permit study team to obtain and use archival tissue, if already existing, or, be willing to undergo a fresh tumor biopsy if clinically possible (exceptions may be provided by study PI if medically unsafe to perform biopsy).
- •Weight ≥ 40 kg
- •ANC ≥ 1500/mm3; platelets ≥ 100,000/mm3
- •AST, ALT ≤ 1.5 x ULN. Patients with liver metastases ≤ 3 x ULN
- •Total serum bilirubin ≤ 1.5 x ULN
- •Creatinine clearence ≥ 60 mL/min
排除标准
- •Current or planned use of Warfarin, Cyclosporine A, Rifampicin, Glyburide (other diabetic medications are allowed)
- •Current or planned use of agents contraindicated for use with strong CYP3A4 inducers
- •Strong inhibitors or inducers of CYP2C9
- •Strong inhibitors or inducers of CYP3A
- •Agent or agents that moderately inhibit both CYP2C9 and CYP3A (via a single concomitant agent, or co-administration of concomitant agents)
- •No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
- •Current or history of ≥ Grade 2 peripheral neuropathy
- •Known allergy to eggs or any of the components within the study agents and/or their excipients.
研究组 & 干预措施
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9
Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Bosentan (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9
Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9
Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Nab-paclitaxel (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9
Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12
Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12
Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21
Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21
Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12
Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Nab-paclitaxel (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21
Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Nab-paclitaxel (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9
Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12
Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Bosentan (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12
Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21
Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Bosentan (Drug)
Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21
Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles.
Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 30 days after last dose of protocol therapy
Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
Dose limiting toxicities (DLTs)
时间窗: Up to 21 days (Cycle 1)
Toxicities will be graded according to NCI CTCAE v 4.0. DLT's apply only to bosentan-only single stage AND cycle 1 and should be attributable to the treatment.
Compliance
时间窗: During the first week
Number of bosentan tablets and bottles returned will be reconciled with the patient diary.
次要结局
- Overall survival (OS)(Time to death as a result of any cause, assessed up to 2 years)
- Progression-free survival (PFS)(Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years)
- Time to treatment failure (TTF)(Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years)