A Single-Arm Feasibility Study of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Resectable Oncologically High-Risk Intrahepatic Cholangiocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 7
- 主要终点
- Number of Participants Who Completed All Preoperative and Operative Therapy
研究概览
简要总结
This phase II trial studies how well gemcitabine, cisplatin, and nab-paclitaxel work before surgery in treating participants with high-risk bile duct cancer in the liver (intrahepatic cholangiocarcinoma). Drugs used in chemotherapy, such as nab-paclitaxel, cisplatin, and gemcitabine, 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 combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
详细描述
PRIMARY OBJECTIVE:
To assess the feasibility of therapeutic approach that includes neoadjuvant chemotherapy including gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel for high-risk but technically resectable intrahepatic cholangiocarcinoma and is completed with surgical resection.
SECONDARY OBJECTIVES:
I. To assess the radiological response rate to neoadjuvant systemic chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST).
II. To determine the R0 resection rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of intrahepatic cholangiocarcinoma.
- •High-quality cross-sectional imaging by computerized tomography (CT) or magnetic resonant imaging (MRI) performed within 6 weeks prior to enrollment and showed a resectable, but high-risk, intrahepatic cholangiocarcinoma (IHCCA) confined to the liver, bile duct, and/or regional lymph nodes. Tumors will be considered high-risk if the high-quality, contrast-enhanced CT and/or MRI +/- positron emission tomography (PET) scan showed: (must meet at least one of the criteria below)
- •T-stage ≥ Ib (Ib-IV)
- •Solitary lesion > 5 cm
- •Multifocal tumors or satellite lesions present confined to the same lobe of the liver as the dominant lesion but still technically resectable
- •Presence of major vascular invasion but still technically resectable
- •Suspicious or involved regional lymph nodes (N1)
- •No distant extrahepatic disease (M0)
- •Able to give informed consent.
- •Able to adhere to study visit schedule and other protocol requirements.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
- •Platelet count ≥ 100,000 cells/μL
- •Hemoglobin ≥ 9 g/dL
- •Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
- •Albumin ≥ 3 g/dL
- •Creatinine ≤ 1.5 x ULN
- •Non-pregnant and non-lactating.
- •Women of child-bearing potential (defined as a sexually mature woman who [1] has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/cisplatin/nab-paclitaxel (including dose interruptions) until treatment with gemcitabine/cisplatin/nab-paclitaxel is complete.
- •Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/cisplatin/nab-paclitaxel and for 6 months following gemcitabine/cisplatin/nab-paclitaxel discontinuation, even if he has undergone a successful vasectomy.
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 (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 cancer, except non-melanoma 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
Gemcitabine, cisplatin, nab-paclitaxel
Participants receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
干预措施: Cisplatin (Drug)
Gemcitabine, cisplatin, nab-paclitaxel
Participants receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
干预措施: Gemcitabine (Drug)
Gemcitabine, cisplatin, nab-paclitaxel
Participants receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Number of Participants Who Completed All Preoperative and Operative Therapy
时间窗: Up to 12 weeks after study start
Completion of all therapy rate will be recorded.
Number of Participants With Adverse Events
时间窗: Up to 3 years after study start
Will be monitored using method of Thall, Simon and Estey, and will be tabulated by the maximum reported Common Terminology Criteria for Adverse Events (CTCAE) grade.
次要结局
- Radiological Response Rate Defined as the Percentage of Patients Who Will Have Complete Response (CR), Partial Response (PR) or Stable Disease (SD) After the Neoadjuvant Therapy(Up to 12 weeks after study start)
- Recurrence-free Survival (RFS)(From the date of surgery up to 3 years)
- Number of Participants With Overall Survival(From date of neoadjuvant treatment start up to 3 years)
研究者
Shishir Kumar Maithel
Principal Investigator
Emory University