Surufatinib Combined With Toripalimab and HAIC in the Treatment of Inoperable or Metastatic Intrahepatic Cholangiocarcinoma

NCT06313554 | Not Yet Recruiting

• 1 other identifier: HMPL-012-SH-ICC101
• Study Type: interventional
• Target: 63
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• ORR objective response rate

  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.

  24 months

Secondary Outcomes (4)

• Progression-Free Survival(PFS)

  24 months

• OS overall survival

  24 months

• DCR disease control rate

  24 months

• Adverse events as assessed by NCI CTCAE v5.0

  24 months

Study Arms (1)

Surufatinib Combined With Toripalimab and HAIC

EXPERIMENTAL

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).

Drug: Surufatinib、Toripalimab、Gemcitabine、Oxaliplatin

Interventions

Surufatinib、Toripalimab、Gemcitabine、Oxaliplatin DRUG

The first week dose of Surufatinib 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).

Surufatinib Combined With Toripalimab and HAIC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L, platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;
• International Standardized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5× upper limit of normal (ULN);
• Liver function: serum total bilirubin ≤ 2 x ULN; ALT/AST ≤ 2 x ULN; Serum albumin ≥28g/L;
• Renal function: serum creatinine ≤ 1.5 x ULN or eGFR≥60%, creatinine clearance (CCr) ≥60mL/min; To rule out urinary system infection, urine routine showed urine protein \< 2+, ≥2+ patients should be collected 24 hours of urine protein volume \< 1g;
• Normal cardiac function with left ventricular ejection fraction (LVEF)≥50% as measured by two-dimensional echocardiography;

You may not qualify if:

• 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;
• The patient currently has medically uncontrolled hypertension, defined as: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
• Urine routine indicated urinary protein ≥2+, and 24-hour urinary protein volume \&gt; 1.0g;
• Patients whose tumors are judged by the investigators to be at high risk of invading vital blood vessels and causing fatal massive bleeding during the follow-up study;
• Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding within 3 months \&gt; 30 mL, hematemesis, stool, stool blood), hemoptysis (within 4 weeks \&gt; 5 mL fresh blood); People with a history of inherited or acquired bleeding or coagulation disorders. There were clinically significant bleeding symptoms or definite bleeding tendencies within 3 months prior to enrollment, such as gastrointestinal bleeding and hemorrhagic gastric ulcer;
• Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure \&gt; Level 2; Ventricular arrhythmias requiring medical treatment; Electrocardiogram (ECG) showed QT c interval ≥480 ms;

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Lu Wang

CONTACT

136 0167 8615; cms024mm@163.com

Ti zhang

CONTACT

180 1731 0060; zhangti@shca.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of liver surgery department

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: March 15, 2024
• Study Start: May 20, 2024
• Primary Completion: May 20, 2024
• Study Completion (Estimated): May 20, 2027
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share