Clinical trial NCT04077983: Nab-Paclitaxel Combined With Gemcitabine Adjuvant Chemotherapy After Radical Resection of Intrahepatic Cholangiocarcinoma
Official title: a Single-arm Study of Nab-Paclitaxel Combined With Gemcitabine Adjuvant Chemotherapy After Radical Resection of Intrahepatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cholangiocarcinoma, Intrahepatic
Keywords: intrahepatic cholangiocarcinoma
nab-paclitaxel and gemcitabine chemotherapy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2019-09-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: PREVENTION

Brief summary: In this phase 2 study, we aim to evaluate the effects and safety of combined therapy using nab-paclitaxel and gemcitabine chemotherapy for patients after radical resection of Intrahepatic Cholangiocarcinoma

Detailed description: Most patients with intrahepatic cholangiocarcinoma (ICC) are often accompanied by local or distant metastases and lose the opportunity for surgical resection. Surgical resection is the only effective means for long-term survival of patients with intrahepatic cholangiocarcinoma. However, multiple tumors, lymph node metastasis, and vascular invasion significantly reduced postoperative survival. Most patients will relapse due to less clinical data. The best adjuvant treatment strategy and standard protocol for patients with intrahepatic cholangiocarcinoma has not been determined. Current treatment options include chemotherapy based on fluoropyrimidine or gemcitabine. Albumin-bound paclitaxel(nab-paclitaxel) has been used to treat a variety of malignancies such as non-small cell lung cancer, pancreatic cancer, breast cancer, melanoma, ovarian cancer and the like. In the field of pancreatic cancer, studies have confirmed that albumin-bound paclitaxel has synergistic effects with gemcitabine. The combination of gemcitabine alone significantly increased the intratumoral concentration of gemcitabine. Albumin-bound paclitaxel plus gemcitabine is the first choice for first-line treatment of pancreatic cancer, but clinical studies in the field of cholangiocarcinoma are very limited. Based on the same origin of pancreatic and biliary embryos, biological behavior and pathological similarities. Therefore, in this second phase of the study, our aim was to evaluate the efficacy and safety of chemotherapy with nab-paclitaxel and gemcitabine in the prevention of postoperative recurrence in patients with intrahepatic cholangiocarcinoma.

Eligibility criteria: Inclusion Criteria:

1. The patient must have good compliance, be understood the research process of this study and required to sign an informed consent form;
2. age 18-75 years old, male or female;
3. Histopathologically confirmed intrahepatic cholangiocarcinoma，excluding mixed liver cancer;
4. The longest diameter of a single tumor in patients before surgery is 3\~9cm. If the number of multiple tumors is ≤3, the total diameter≤9cm, maximum diameter ≤5cm;
5. Study treatment can be started within 4\~6 weeks after R0 resection;
6. Except for R0 resection, no other anti-tumor treatment has been received;
7. No distant transfer；
8. ECOG\<2, or KPS\>70；
9. Bone marrow function criteria: hemoglobin (HGB)≥90g/L; absolute neutrophil count (ANC)≥1.5×109/L; platelets (PLT)≥100×109/L;
10. Liver function criteria: ALT, AST≤5×ULN, serum total bilirubin\<3×ULN;
11. Renal function criteria: creatinine clearance \> 45 mL/min
12. Prothrombin time \<14s; (no anticoagulant therapy);
13. Patients without biliary obstruction who require biliary stent implantation must be completed at least 7 days prior to enrollment;
14. Non-lactating or pregnant women, contraception during or after 6 months of treatment.
15. No contraindications for gemcitabine and Nab-paclitaxel.

Exclusion Criteria:

1. Those patients who are allergic to the chemotherapy drugs and their components in this study
2. Patients with other malignant tumors within 5 years (except for cured carcinoma in situ or basal cell carcinoma of the skin)
3. Concomitant diseases that may interfere with treatment studies: such as severe infections, HIV-positive, clinically severe (ie active) Heart disease, uncontrolled epilepsy, central nervous system disease, or history of mental disorders;
4. Intraoperative or postoperative pathology determines patients who do not meet radical resection;
5. Patients with current or previous ≥ grade II peripheral neuropathy;
6. Patients who participated in other clinical studies within 4 weeks prior to enrollment;
7. Patients who has undergone organ transplantation;
8. Patients considered by the investigator not suitable for this trial.

Primary outcomes:
measure: Disease-free survival
timeFrame: 24 months
Secondary outcomes:
measure: safety: the potential side effects
timeFrame: 6 months
Other outcomes:
measure: overall survival
timeFrame: 24 months
Locations:
Study officials:
affiliation: Fudan University
name: Jian Zhou, MD&PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D, Noker P, Yao R, Labao E, Hawkins M, Soon-Shiong P. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 2006 Feb 15;12(4):1317-24. doi: 10.1158/1078-0432.CCR-05-1634.
citation: Frese KK, Neesse A, Cook N, Bapiro TE, Lolkema MP, Jodrell DI, Tuveson DA. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov. 2012 Mar;2(3):260-269. doi: 10.1158/2159-8290.CD-11-0242. Epub 2012 Feb 28.
citation: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.