A Single-Arm Phase II Clinical Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma
概览
- 阶段
- 2 期
- 干预措施
- Biopsy
- 疾病 / 适应症
- Resectable Pancreatic Adenocarcinoma
- 发起方
- Emory University
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Clinical Response Rate to Neoadjuvant Chemotherapy
- 状态
- 招募中
- 最后更新
- 10天前
概览
简要总结
This phase II trial tests how well gemcitabine, cisplatin and nab-paclitaxel given before surgery (neoadjuvant) works in treating patients with pancreatic cancer that can be removed by surgery (resectable) or that is borderline resectable. The standard treatment for resectable and borderline resectable pancreatic cancer is a combination of surgery and chemotherapy. Neoadjuvant therapy is more feasible and could improve outcomes compared to patients receiving surgery first. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel, an antimicrotubule agent that stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel may have fewer side effects and work better than other forms of paclitaxel. Gemcitabine, cisplatin and nab-paclitaxel may be an effective neoadjuvant treatment option for patients with resectable or borderline resectable pancreatic cancer.
详细描述
PRIMARY OBJECTIVE: I. Determine the major pathological response rate, feasibility and safety of biweekly gemcitabine, cisplatin and nab-paclitaxel (GCN) in the neoadjuvant setting for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma. SECONDARY OBJECTIVE: I. Determine if neoadjuvant GCN increases tumoral infiltration of lymphocytes with local and systemic phenotypic features that assist in the antitumor immune response. OUTLINE: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) at pre-study and on study. After completion of study treatment, patients are followed up every 3-4 months for up to 24 months.
研究者
Hussein Hamad
Principal Investigator
Emory University
入排标准
入选标准
- •Histologically or cytologically confirmed - resectable and borderline resectable pancreatic ductal adenocarcinoma
- •Resectability will be defined as per National Comprehensive Cancer Network (NCCN) guidelines using cross-sectional imaging (contrast-enhanced computed tomography or magnetic resonance imaging scans of the abdomen, and pelvis)
- •Decisions about resectability status will be made in consensus at multidisciplinary meetings/discussions
- •Resectable disease will be defined as:
- •No interface of the tumor with celiac artery, common hepatic artery (CHA), or superior mesenteric arteries (SMA) (and, if present, variants)
- •Less than 180° interface between tumor and vessel wall of the portal or superior mesenteric veins (SMV) without vein contour irregularity
- •For tumors of the body and tail of the pancreas, interface with the splenic artery and splenic vein of any degree will be considered resectable disease
- •Borderline resectable disease will be defined as:
- •To include at least one of the following:
- •Tumor abutment \< 180° of the superior mesenteric artery or celiac axis
排除标准
- •Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.
- •In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)"
- •Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations
- •Pregnancy (positive pregnancy test) or lactation
- •Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (radiosurgery \[RS\]; Gamma Knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
- •Previous (within the past 5 years) or concurrent presence of other untreated cancer, except nonmelanoma skin cancer and in situ carcinomas
- •History of allergy or hypersensitivity to any of the study drugs
- •Current abuse of alcohol or illicit drugs
- •Inability or unwillingness to sign the informed consent form
研究组 & 干预措施
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Biopsy
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Biospecimen Collection
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Computed Tomography
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Magnetic Resonance Imaging
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Pancreatic Surgical Procedure
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Nab-paclitaxel
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Cisplatin
Treatment (nab-paclitaxel, cisplatin, gemcitabine)
Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.
干预措施: Gemcitabine
结局指标
主要结局
Clinical Response Rate to Neoadjuvant Chemotherapy
时间窗: Up to 24 months
Clinical response is defined as biochemical, radiological, pathological response or stable disease. • Biochemical response (or CA 19-9 response) is defined as \>50% decrease from baseline with tumor response. Radiologic response is defined as complete response (CR), partial response (PR) or stable disease (SD) after the neoadjuvant therapy per RECIST 1.1. Pathologic response is defined by CAP scoring system as 0 (complete response), 1 (moderate response), 2 (minimal response) and 3 (poor or no response). Stable disease is defined as the absence of biochemical response (\>50% CA 19-9 reduction), radiological response (per RECIST 1.1), or major pathological response (CAP Score 0-1), without metastasis / unresectability, and patient undergoes surgical resection. Clinical response rate (including clinical, biochemical, radiological, pathological response or stable disease) will be reported as a proportion, with an exact 90% confidence interval estimated using the Clopper-Pearson method.
次要结局
- Radiologic Response Rate(Up to 24 months)
- Recurrence-Free Survival (RFS)(From surgery to recurrence or death, assessed up to 24 months)
- Treatment Completion(Up to 24 months)
- Pathological Response Rate(Up to 24 months)
- R0 Resection Rate(At time of surgery)
- Nodal Status(Up to 24 months)
- Overall Survival (OS) Rate(From study treatment start to date of death, assessed up to 24 months)
- Carbohydrate Antigen (CA)19-9 response(Up to 24 months)
- Incidence of Adverse Events (AEs)(Up to 28 days after last dose of study treatment)
- Neoadjuvant Systemic Chemotherapy Rate(Up to 4 months)