Nab-Paclitaxel Combined With Gemcitabine Adjuvant Chemotherapy After Radical Resection of Intrahepatic Cholangiocarcinoma

Phase 2

• Conditions: Cholangiocarcinoma, Intrahepatic
• Interventions: Drug: combined therapy using nab-paclitaxel and gemcitabine chemotherapy

• Registration Number: NCT04077983
• Lead Sponsor: Shanghai Zhongshan Hospital

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.

Study Timeline

• Status Verified: 2019-09
• Study Start: 2019-09-01
• Study First Submitted: 2019-09-01
• Study First Submitted QC: 2019-09-03
• Last Update Submitted: 2019-09-03
• Study First Posted: 2019-09-04
• Last Update Posted: 2019-09-04
• Primary Completion: 2020-09-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
combined therapy using nab-paclitaxel and gemcitabine chemo	combined therapy using nab-paclitaxel and gemcitabine chemotherapy	1. Day1 nab-paclitaxel 125mg/m2, Day8 nab-paclitaxel 125mg/m2 2. Day1 gemcitabine 1000mg/m2, Day8 gemcitabine 1000mg/m2 3. Three weeks is a course of treatment with a total of 4 courses.

Primary Outcome Measures

Name	Time	Method
Disease-free survival	24 months	the time from the day after surgery to the recurrence of cancer.

Secondary Outcome Measures

Name	Time	Method
safety: the potential side effects	6 months	the potential side effects