HAIC Combined Sintilimab for Liver Metastasis From Esophageal Squamous Cell Carcinoma

Hepatic Arterial Infusion Chemotherapy Combined Sintilimab for Predominant Liver Metastasis From Esophageal Squamous Cell Carcinoma- A Pilot Study

Patients with liver metastasis from esophagus squamous (ESC) are usually offered systemic therapy. However, for those with predominant liver disease or failure of system therapy, local liver management becomes an option. This prospective single center study aimed to evaluate the efficacy and adverse events of hepatic arterial infusion chemotherapy (HAIC) using percutaneous catheter placement techniques for liver metastases from esophagus squamous (ESC).

Study Overview

• Status: Completed
• Conditions: Liver Metastases; Esophageal Squamous Cell Carcinoma; Hepatic Arterial Infusion Chemotherapy
• Intervention / Treatment: Drug: HAIC combined with intravenous PD-1

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Both male and female, aged 18-75 years;
2. ECOG score 0-1;
3. Pathological diagnosis: metastatic esophageal squamous cell carcinoma confirmed by histological or cytological examination (excluding adenosquamous carcinoma mixed type and other pathological types).
4. Metachronous liver metastasis after esophagectomy, especially when liver was the only metastatic organ, or synchronous liver metastasis progressed after first-line medical treatment; Or liver metastasis is currently the main threat, and control of liver metastasis should be the main goal
5. predicted survival time ≥3 months.
6. Liver function: Child-Pugh score 5-7. ALT, AST, ALP< 2.5 times upper limit of normal, total bilirubin< 1.5 times upper limit of normal, PT, INR were < 1.5 times upper limit of normal, respectively. Bone marrow function was good (white blood cell ≥3.0 x 109/L, granulocyte ≥1.5 x 109/L, platelet ≥75 x 109/L, HGB≥100g/l), renal function was good (BUN < 40mg/dl, creatinine < 2mg/ml).
7. HBV infection, should have effective antiviral treatment, HBV DNA < 100IU/ml.
8. agree to be enrolled in the study, be willing to cooperate with the clinical research, and sign the informed consent.
9. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age should use effective contraception during the entire treatment period and for 6 months after the treatment period.

Exclusion Criteria:

1. age > 75 years old;
2. ECOG score ≥2;
3. poor liver function, Child-Pugh score > 7, or liver enzyme, coagulation, bilirubin and bone marrow function did not meet the inclusion criteria.
4. History of esophagogastric bleeding, hepatic encephalopathy, massive ascites, and abdominal infection.
5. lung, bone, mediastinal lymph nodes, multiple lower abdominal lymph nodes, pelvic lymph nodes and other distant metastases, unable to receive local radiotherapy.
6. The tumor was close to the intestinal tract and other organs, and it was difficult to tolerate interventional therapy; Patients with residual liver volume less than 800ml and difficult to tolerate interventional therapy.
7. allergic to Sintilimab.
8. patients had received previous immunotherapy, such as PD-1 antibody, PD-L1 antibody, CTLA4 antibody.
9. use of immunosuppressive drugs within the previous 4 weeks, excluding intranasal, inhaled, or other topical glucocorticoids or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/ day of prednisone or the equivalent dose of other glucocorticoids), and temporary use of glucocorticoids for the treatment of dyspnea in conditions such as asthma, chronic obstructive pulmonary disease, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: esophageal squamous cell carcinoma with liver metastasis; Patients with esophageal squamous cell carcinoma with liver metastasis have poor response to first-line treatment, especially those with advanced esophageal cancer with progression or recurrence in the liver.	Drug: HAIC combined with intravenous PD-1; Hepatic arterial chemoinfusion (HAIC) was used for interventional therapy with at least 2 cycles of hepatic arterial infusion. The intervention was started with sintilimab at the same time, 200mg each time, and the drug was repeated every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Defined as the proportion of patients with Adverse events (AEs), Treatment Emergent Adverse events (TEAEs), Treatment-related AEs (TRAEs), immune-related AEs (irAEs), adverse events of special interest (AESI) and Serious Adverse events (SAE), assessed by NCI CTCAE v5.0	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate of liver metastases	Defined as proportion of patients who have a best response of CR or PR of liver metastases	Up to 2 years
The overall response rate ( ORR)	Defined as proportion of patients who have a best response of CR or PR	Up to 2 years
The time to response (TTR)	Defined as the time between the date of treatment start and objective tumor response	Up to 2 years
The duration of response (DOR)	Defined as the time from first response (CR or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.	Up to 2 years
The progression free survival (PFS)	Defined as the time from the date of treatment start to disease progression, or death due to any cause, whichever occurs first.	Up to 2 years
The overall survival (OS)	Defined as the time from the date of treatment start to the date of death	Up to 2 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: December 14, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: liver metastasis; hepatic arterial infusion chemotherapy; esophagus carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Head and Neck Neoplasms; Neoplastic Processes; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Neoplasm Metastasis; Carcinoma, Squamous Cell; Liver Neoplasms; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: HAIC FOR LMESC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No