HAIC Combined With Donafenib and Sintilimab for Unresectable ICC

NCT05348811 | Completed Phase 2

• 1 other identifier: CHANCE 2203
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of HAIC combined with donafenib and sintilimab in first-line treatment of unresectable ICC.

Conditions

Cholangiocarcinoma

Keywords

Hepatic arterial infusion chemotherapy; Donafenib; Sintilimab; Intrahepatic cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for unresectable intrahepatic cholangiocarcinoma

  max 24 months

Secondary Outcomes (5)

• Disease control rate (DCR)

  max 24 months

• Duration of response (DOR)

  max 24 months

• Progression-free survival (PFS)

  max 24 months

• Overall survival (OS)

  max 42 months

• Adverse events

  max 42 months

Study Arms (1)

HAIC combined with donafenib and sintilimab

EXPERIMENTAL

HAIC- GEMOX regimen, Day 1, every 3 weeks (Q3W). The maximum of 6 times. Sintilimab will be given on Day 1, 200 mg i.v. Q3W.The longest treatment time is 24 months. Donafenib was taken orally at 0.2 bid on an empty stomach, with an interval of about 12 hours. Donafenib treatment is initiated within 1 to 3 days of each HAIC treatment.

Drug: HAIC combined with donafenib and sintilimab

Interventions

HAIC combined with donafenib and sintilimab DRUG

HAIC- GEMOX regimen, gemcitabine 1000 mg/m2, oxaliplatin 85mg/m2 (if the maximum tumor diameter \> 10cm, the dose is 130mg/m2), the first day of each cycle (D1), Q3W. The maximum of 6 times. Sintilimab will be given on the first day of each cycle (D1). 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.The longest treatment time is 24 months. Donafenib was taken orally at 0.2 bid on an empty stomach (1 hour before or \> 2 hours after meal) in the morning and evening of each administration day, with an interval of about 12 hours. Donafenib treatment is initiated within 1 to 3 days of each HAIC treatment until toxicity is intolerable, the investigator determines disease progression, death, informed consent is withdrawn, new antitumor therapy is initiated, or treatment is discontinued for any other reason specified in the protocol.

Also known as: HAIC-donafenib-sintilimab

HAIC combined with donafenib and sintilimab

Eligibility Criteria

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

You may qualify if:

• Unresectable or metastatic histologically or cytologically confirmed ICC
• No previous systemic treatment or local anti-tumor treatment other than surgery (biliary drainage is allowed), admission was allowed for more than 6 months after the end of adjuvant therapy
• Child-Pugh score ≤7
• Life expectancy ≥ 3 months
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
• Eastern Cooperative Oncology Group(ECOG) performance status (PS) ≤ 1
• The functional indicators of important organs meet the following requirements:
• Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1.5\*10\^9 /L; platelet (PLT) ≥ 80 \*10\^9 /L; hemoglobin (HGB) ≥ 9.0 g/dL
• Bilirubin ≤ 1.5 times upper limits of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times ULN
• Serum creatinine ≤ 1.5 times ULN, and creatinine clearance ≥ 60 ml/min (calculated by Cockcroft-Gault formula)
• International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN
• Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline of TSH is outside the normal range, patients with normal total T3 (or FT3) and free tetraiodothyronine (FT4) can also be enrolled
• The myocardial enzyme profile was within the normal range
• For women who are not breastfeeding or pregnant, use contraception during treatment or 4 months after the end of treatment
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of the trial

You may not qualify if:

• Other malignancies diagnosed within 5 years before the first dose, excluding radically cured basal cell carcinoma of skin, squamous cell carcinoma of skin, and/or radically cured carcinoma in situ.
• Pathological diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, and other malignant components of non-cholangiocarcinoma
• Receipt of treatment in other clinical trials within 4 weeks before the first dose
• Previous receipt of any antibody treatment involving anti-PD-1, anti-PD-L1/L2, or anti-CTLA4 or other immunotherapies
• Previous receipt of targeted drug(s)
• Previous receipt of palliative radiotherapy for biliary tract tumors, except for postoperative adjuvant radiotherapy
• Previous receipt of Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural effusion) within 2 weeks before the first dose
• An active autoimmune disease requiring systemic therapy (e.g., palliative drugs, glucocorticoids, or immunosuppressants) developed within 2 years prior to first administration
• Have received systemic glucocorticoid therapy (excluding nasal spray, inhalation, or other topical glucocorticoid) or any other form of immunosuppressive therapy during the 4 weeks prior to the study
• Obstructive jaundice (active treatment, such as biliary drainage or stent, can be included after liver function recovery)
• Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation is known
• Known allergic patients to sintilimab, the active ingredient of donafinib or excipients of the drug under study
• Not fully recovered from toxicity and/or complications associated with any intervention prior to initiation of treatment (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss)
• Human immunodeficiency virus (HIV), HIV 1/2 antibody positive
• Untreated active hepatitis B (defined as HBsAg positive with hepatitis B virus DNA (HBV-DNA) copy number greater than the ULN in the laboratory department of the research center) \[Note: Hepatitis B patients who meet the following criteria can also be enrolled: 1) HBV DNA \<2.5\*10\^3 copies/ml (500 IU/ml) before the first dose, should receive anti-HBV treatment throughout the study period; patients with anti-hepatitis B core antigen(HBc) (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation needs to be closely monitored\]

Sponsors & Collaborators

• Zhongda Hospital: lead

Study Sites (1)

Zhongda Hospital, Southeast University

Nanjing, Jiangsu, 210009, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

donafenib; sintilimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Gao-Jun Teng

  Zhongda Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dean

Model Details: HAIC (GEMOX regimen) combined with donafenib and sintilimab

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: April 27, 2022
• Study Start: June 13, 2022
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: January 6, 2026

Record last verified: 2022-06

Locations

CN (1)