A Single-center, Single-arm, Open-label Clinical Study of Surufatinib Combined With Toripalimab and HAIC in Patients With Inoperable or Metastatic Intrahepatic Cholangiocarcinoma
Overview
- Phase
- Not Applicable
- Intervention
- Surufatinib、Toripalimab、Gemcitabine、Oxaliplatin
- Conditions
- Intrahepatic Cholangiocarcinoma
- Sponsor
- Fudan University
- Enrollment
- 63
- Primary Endpoint
- ORR objective response rate
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is a single-arm, open-arm, single-center clinical study to explore the efficacy and safety of HAIC in combination with Surufatinib and Toripalimab in patients with inoperable or metastatic intrahepatic cholangiocarcinoma.
The study was divided into three stages: screening period, treatment period and follow-up period. During the treatment period, the tumor status was evaluated by imaging every 6 weeks (±7 days), and the efficacy was changed to every 8 weeks (±7 days) after 12 weeks until the disease progressed (RECIST 1.1) or death (during the treatment of the patient) or toxicity became intolerable. The tumor treatment status and survival status after the disease progression were recorded. Safety outcome measures included AE, changes in laboratory test values, vital signs and electrocardiogram changes.
Investigators
Lu Wang, MD, PhD
Head of liver surgery department
Fudan University
Eligibility Criteria
Inclusion Criteria
- •The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up;
- •Inoperable or metastatic intrahepatic bile duct carcinoma confirmed by histopathology or cytology;
- •In accordance with the NCCN guidelines for intrahepatic cholangiocarcinoma diagnosis criteria, intrahepatic cholangiocarcinoma not suitable for radical resection was confirmed: R0 resection could not be obtained, liver was multiple, lymph node metastasis beyond the hepatic portal area and distant metastasis;
- •Male or female between the ages of 18 and 75 (including boundary values);
- •ECOG score: 0-1; Expected survival ≥12 weeks;
- •Liver function Child-Pugh grade A;
- •Have not received systematic treatment for inoperable or metastatic biliary tract cancer; Patients who had received adjuvant or neoadjuvant chemotherapy of one regimen and relapsed 6 months after the end of chemotherapy could be enrolled;
- •At least one measurable lesion (according to RECIST 1.1); Magnetic resonance imaging (MRI) enhancement or computed tomography (CT) enhancement were used to accurately measure the diameter of the lesion ≥1cm, and the study target lesion had not previously received local treatment (including but not limited to HIAC, radiofrequency ablation, argon helium knife, radiation therapy and other local treatments);
- •No serious organic diseases of heart, lung, brain and other organs;
- •The main organs and bone marrow functions are basically normal:
Exclusion Criteria
- •Participated in clinical trials of other anti-tumor drugs within 4 weeks before enrollment;
- •Patients with a history of TACE treatment and who had previously received any immune or targeted therapy were excluded; Patients with a history of hepatectomy, postoperative recurrence, and no systemic therapy were included
- •The investigators determined that liver metastases accounted for 90% or more of the total liver volume;
- •Patients who have previously received an organ transplant or are planning an organ transplant;
- •Patients with obstructive jaundice but yellowing is not as expected;
- •Have had other malignancies within the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
- •Patients who have had or are currently having any brain metastases;
- •Other strong inducers or suppressors of CYP3A4 were taken within 2 weeks prior to the first study;
- •Received any surgery (except biopsy) or invasive treatment or operation within 4 weeks before enrollment, and the surgical incision was not completely healed (except intravenous catheterization, puncture drainage, etc.);
- •Electrolyte abnormalities identified by the investigator as clinically significant;
Arms & Interventions
Surufatinib Combined With Toripalimab and HAIC
The first week dose of solantinib was 150mg, the second week and the subsequent cycle was 200 mg once a day (QD) orally, Q3W, and the drug was suspended for one day on the day of HAIC; Toripalimab: 240mg intravenous infusion d1, Q3W; HAIC: All patients received HAIC treatment on D1. Hepatic arterial perfusion therapy (HAIC) : a treatment cycle every 3 weeks for 4-6 consecutive cycles: Surufatinib and Toripalimab were administered continuously until intolerable toxicity, disease progression, withdrawal of informed consent, loss of follow-up, and investigator judgment that medication should be discontinued (whichever occurred first).
Intervention: Surufatinib、Toripalimab、Gemcitabine、Oxaliplatin
Outcomes
Primary Outcomes
ORR objective response rate
Time Frame: 24 months
objective response rate (ORR)Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Secondary Outcomes
- OS overall survival(24 months)
- Adverse events as assessed by NCI CTCAE v5.0(24 months)
- Progression-Free Survival(PFS)(24 months)
- DCR disease control rate(24 months)