Neoadjuvant Immune-Checkpoint Blockade Therapy Combining With TACE For Resectable Hepatocellular Carcinoma With High Recurrence Risk: A Phase II, Single-arm Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Cadonilimab
- Conditions
- Resectable Hepatocellular Carcinoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 54
- Primary Endpoint
- Major Pathological Response Rate (MPR rate)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase 2, open-label, single-arm study of neoadjuvant immune-checkpoint blockade therapy (AK104) combining with TACE for resectable hepatocellular carcinoma. The purpose is to investigate the efficacy and safety of this therapeutic regimen to reduce the risk of postoperative recurrence in resectable HCC patients with a high risk of recurrence.
Detailed Description
The trial will recruit 54 patients. At the first step, 26 patients will be recruited. Only when at least 10 patients achieve major pathological response after surgery will the trial enter the second step and continue to recruit other patients. After being enrolled, all patients giving written informed consent will receive TACE plus 2-cycle of Cadonilimab treatment before surgery. Four weeks later after surgery, Cadonilimab treatment will be followed up to 16 cycles. The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow up will be conducted as well.
Investigators
Ming Kuang
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years but ≤75 years
- •Resectable HCC staged BCLC A/B
- •Treatment naïve for HCC
- •High risk for recurrence, meeting at least one of the following criteria:
- •Multiple tumor lesions
- •Individual tumor \> 5cm
- •AFP \> 400 ug/L
- •MVI positive based on preoperative MRI according to MVI predictive model of Radiomics
- •Measurable or evaluable lesions according to RECIST v1.1 criteria
- •ECOG performance status 0-1
Exclusion Criteria
- •Any prior treatment for HCC.
- •Tumor rupture or bleeding. Suspected abdominal metastasis.
- •A major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to enrollment.
- •History of allogenic organ transplantation.
- •Under other clinical trials.
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: vitiligo or alopecia, hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement, any chronic skin condition that does not require systemic therapy or celiac disease controlled by diet alone.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to AK104 or other immune checkpoint inhibitors.
- •Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (including tuberculosis), uncontrolled hypertension (defined as blood pressure of \> 140/90 mmHg during the screening period despite medical management), interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
- •History of hepatic encephalopathy, refractory ascites or esophagogastric varices with high risk of bleeding. Upper gastrointestinal hemorrhage within the year prior to the first dose of study drug.
- •Active hepatitis B infection without treatment (positive HBV surface antigen (HBsAg) and HBV DNA ≥ 1000 IU/ml). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Active hepatitis C infection (positive HCV antibody and HCV RNA above the lower limit of detection).
Arms & Interventions
TACE+Cadonilimab+Surgery
After appropriate screening and randomization, patients enrolled will receive TACE plus 2-cycle of Cadonilimab treatment before surgery. Four weeks later after surgery, Cadonilimab treatment will be followed up to 16 cycles.
Intervention: Cadonilimab
TACE+Cadonilimab+Surgery
After appropriate screening and randomization, patients enrolled will receive TACE plus 2-cycle of Cadonilimab treatment before surgery. Four weeks later after surgery, Cadonilimab treatment will be followed up to 16 cycles.
Intervention: TACE
TACE+Cadonilimab+Surgery
After appropriate screening and randomization, patients enrolled will receive TACE plus 2-cycle of Cadonilimab treatment before surgery. Four weeks later after surgery, Cadonilimab treatment will be followed up to 16 cycles.
Intervention: Surgery
Outcomes
Primary Outcomes
Major Pathological Response Rate (MPR rate)
Time Frame: Up to 2 years
MPR rate is defined as the percentage of patients with over 90% of histological tumor tissue necrosis removed after neoadjuvant TACE combined with AK104 treatment.
Secondary Outcomes
- 1-year recurrence rate(The percentage of patients who suffer recurrence one year after surgery.)
- Objective response rate (ORR)(ORR is defined as the percentage of patients who have achieved complete response (CR) or partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after neoadjuvant TACE combined with AK104 treatment but before)
- Incidence of Adverse Events (AE)(The percentage of patients who suffer grade 3 or worse adverse events from the first dose of administration to last follow-up, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.)