HAIC Combined With Cadonilimab and Regorafenib as 2nd-line Treatment for ICC

NCT06335927 | Recruiting Phase 2

• 1 other identifier: GWK2023-001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm Phase II clinical trial aiming to evaluate the safety and efficacy of HAIC combined with Cadonilimab and Regorafenib as second-line treatment for unresectable intrahepatic cholangiocarcinoma. The study plans to enroll approximately 45 participants. All enrolled participants will receive continuous treatment: HAIC-Gemox: Gemcitabine 1000mg/m2 on Day 1 + Oxaliplatin 85mg/m2 on Day 1, every 3 weeks (Q3W), for up to 6 treatment cycles, Cadonilimab(6mg/kg, D2, Q3W) and Regorafenib (80mg QD, Q3W) until the investigator determines that there is no longer any clinical benefit (based on comprehensive assessment including RECIST v1.1 imaging evaluation and clinical condition), intolerable toxicity, initiation of new anti-tumor therapy, or meeting other criteria for treatment discontinuation, whichever occurs first.

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

HAIC; Cadonilimab; Regorafenib; Second-line; Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR), based on RECIST v1.1 assessment.

  54 weeks

Secondary Outcomes (7)

• Hepatic Objective Response Rate (hORR)

  54 weeks

• Duration of Response (DoR)

  54 weeks

• Disease Control Rate (DCR)

  54 weeks

• Time to Response (TTR)

  54 weeks

• Progression-Free Survival (PFS)

  54 weeks

Study Arms (1)

HAIC-GEMOX+Cadonilimab+Regorafenib

EXPERIMENTAL

HAIC-GEMOX: Gemcitabine 1000mg/m2 on Day 1 + Oxaliplatin 85mg/m2 on Day 1, every 3 weeks (Q3W), for up to 6 treatment cycles in combination with Cadonilimab (6mg/kg, D2, Q3W) and Regorafenib (80mg QD, Q3W)

Drug: HAIC-GEMOX+Cadonilimab+Regorafenib

Interventions

HAIC-GEMOX+Cadonilimab+Regorafenib DRUG

HAIC-GEMOX: Gemcitabine 1000mg/m2 on Day 1 + Oxaliplatin 85mg/m2 on Day 1, every 3 weeks (Q3W), for up to 6 treatment cycles in combination with Cadonilimab (6mg/kg, D2, Q3W) and Regorafenib (80mg QD, Q3W)

HAIC-GEMOX+Cadonilimab+Regorafenib

Eligibility Criteria

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

You may qualify if:

• Voluntarily provide written informed consent.
• Age at enrollment is ≥18 years and ≤75 years, both males and females.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival period of ≥3 months.
• Patients with histologically or cytologically confirmed unresectable intrahepatic cholangiocarcinoma. Patients who have failed standard treatment (standard treatment includes gemcitabine plus cisplatin plus pembrolizumab, gemcitabine plus gemcitabine plus oxaliplatin, capecitabine plus oxaliplatin, chemotherapy mainly based on albumin-bound paclitaxel, 5-fluorouracil (5-FU) plus platinum-based therapy) or are intolerant to standard treatment, or patients for whom standard treatment is not accessible. Note: Patients who have received adjuvant/neoadjuvant chemotherapy targeting non-metastatic disease with curative intent and experience disease progression within ≤6 months after the last treatment are eligible.
• At least one measurable lesion according to RECIST v1.1 that can be accurately measured repeatedly. Note: Brain metastases cannot be considered as target lesions.
• Adequate organ function determined by the following requirements:
• Hematology (no use of any blood components or growth factors within 7 days prior to starting the study treatment): i. Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L (1,500/mm3). ii. Platelet count ≥ 80 × 109/L (100,000/mm3). iii. Hemoglobin ≥ 90 g/L.
• Kidney:
• i. Serum creatinine ≤ 1.5 × Upper Limit of Normal (ULN). ii. Calculated creatinine clearance\* (CrCl) ≥ 50 mL/min.
• \* CrCl will be calculated using the Cockcroft-Gault formula (Cockcroft-Gault formula).
• CrCl (mL/min) = {(140 - age) × body weight (kg) × F} / (SCr (mg/dL) × 72) For males, F = 1; for females, F = 0.85; SCr = serum creatinine. iii. Urine protein ≤ 1+ or 24-hour urinary protein quantification \< 1.0 g. c) Liver: i. Total bilirubin (TBil) ≤ 3 × ULN. ii. AST and ALT ≤ 5 × ULN. iii. Serum albumin (ALB) ≥ 28 g/L. d) Coagulation function: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (unless the subject is receiving anticoagulant therapy and coagulation parameters \[PT/INR and APTT\] are within the expected range for anticoagulant treatment at screening).
• e) Cardiac function: i. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• Female participants of childbearing potential must undergo urine or serum pregnancy testing within 3 days prior to the first dose of study medication (if the urine pregnancy test results cannot be confirmed as negative, a serum pregnancy test must be conducted, with the serum pregnancy test result being definitive). If female participants of childbearing potential engage in sexual activity with a nonsterilized male partner, they must use an acceptablemethod of contraception from the start of screening and agree to continue using contraception for up to 120 days after the last dose of the study medication. The decision to stop contraception after this time should be discussed with the investigator.
• Male participants with a female partner of childbearing potential must use effective contraception from the start of screening until 120 days after the last dose of the study medication. The decision to stop contraception after this time should be discussed with the investigator.

You may not qualify if:

• Subjects meeting any of the following criteria will be ineligible to participate in this study:
• Diagnosis of malignant tumors with non-biliary cancers such as hepatocellular carcinoma, mixed-cell carcinoma, or fibrolamellar carcinoma.
• History of other malignant tumors within the past 3 years, except for cured localized tumors (e.g., basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ).
• Concurrent participation in another clinical study unless it is an observational, non-interventional study or follow-up period of an interventional study.
• Palliative local therapy performed on non-target lesions within 2 weeks prior to the first dose; non-specific immune modulating therapy (e.g., interleukins, interferons, thymosin, excluding IL-11 for thrombocytopenia) within 2 weeks prior to the first dose; use of traditional Chinese medicine or herbal remedies with anti-tumor indications within 1 week prior to the first dose.
• Previous receipt of any immune anti-tumor therapy, including immune checkpoint stimulants (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies), immune cell therapy.
• Previous receipt of targeted therapy.
• Active autoimmune diseases requiring systemic treatment within the past two years (e.g., medications for disease improvement, corticosteroids, immunosuppressive therapy); replacement therapy (e.g., thyroid hormones, insulin, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment.
• History of active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
• History of immunodeficiency; positive HIV antibody test; current long-term use of systemic corticosteroids or other immunosuppressive agents.
• Known active tuberculosis (TB) or suspected active TB requiring clinical evaluation; known active syphilis infection.
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• History of or current non-infectious pneumonitis/interstitial lung disease requiring systemic corticosteroid therapy.
• Severe infection within 4 weeks prior to the first dose, including complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective treatment within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or C).
• Subjects with active hepatitis B (positive HBsAg and HBV-DNA \>1000 copies/mL \[200 IU/mL\] or above the lower limit of detection, whichever is higher). Note: Subjects with hepatitis B should receive antiviral therapy during the study treatment period.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Lu Wang, M.D.

CONTACT

+8618121299357; w.lr@hotmail.com

Li Tan

CONTACT

+86 158 0068 0751

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: Director of Hepatobiliary Surgery

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: March 28, 2024
• Study Start: May 11, 2023
• Primary Completion: May 10, 2025
• Study Completion: May 10, 2026
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

CN (1)