The Combination Therapy of TACE and Ablation With Durvalumab in Hepatocellular Carcinoma at Intermediate Stage (TAD)

NCT04517227 | Unknown

• 1 other identifier: ESR-19-20285
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a pilot study with a single arm in a single center assessing safety and efficacy of combination therapy of TACE and ablation and durvalumab. This study will be conducted in selected patients with intermediate stage HCC not amenable to curative therapy.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (4)

• Adverse events

  safety

  From date of the first treatment until 90 days after the last treatment, assessed up to 21 months

• Serious adverse events

  safety

  From date of the first treatment until 90 days after the last treatment, assessed up to 21 months

• AEs of Special Interest

  safety

  From date of the first treatment until 90 days after the last treatment, assessed up to 21 months

• Discontinue rate caused by any AEs

  safety

  From date of the first treatment until date of the last treatment, assessed up to 18 months

Secondary Outcomes (5)

• Progression-free survival (mRECIST) by IRRC

  From date of the first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• Time to progress (mRECIST) by IRRC

  From date of the first treatment until the date of first documented progression, assessed up to 36 months

• PFS rate at 12 months (mRECIST) by IRRC

  From date of the first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• PFS rate at 24 months (mRECIST) by IRRC

  From date of the first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Overall survival

  From date of the first treatment to the date of death, assessed up to 36 months

Study Arms (1)

single arm

EXPERIMENTAL

All patients enrolled with receive the sequential therapy of TACE, ablation and durvalumab.

Drug: Durvalumab; Procedure: Transcatheter Hepatic Arterial Chemoembolization (TACE); Procedure: Ablation

Interventions

Durvalumab DRUG

Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1 and is being developed by AstraZeneca/MedImmune for use in the treatment of cancer.

Also known as: IMFINZI

single arm

Transcatheter Hepatic Arterial Chemoembolization (TACE) PROCEDURE

TACE techniques have been described in the NCCN and ESMO-ESDO guidelines, including cTACE and DEB-TACE.

single arm

Ablation PROCEDURE

In this study, thermal ablation could be conducted with radiofrequency (RFA) or microwave (MWA).

single arm

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years.
• Have a HCC diagnosis confirmed by radiology, histology, or cytology. Note: Radiologic confirmation diagnosis is provided by the study site. Definition of radiological confirmation: Clinical findings consistent with the diagnosis of a liver mass measuring at least 1 cm with characteristic vascularization (intense enhancement seen in the hepatic arterial-dominant phase and contrast washout in the late portal venous phase) seen in either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI).
• HCC newly diagnosed or recurrent with a history of surgery or ablation, with Barcelona Clinic Liver Cancer (BCLC) Stage B not amenable to curative surgery or transplantation or that the patient refuses surgery.
• At least 1 measurable intrahepatic lesion (≥1.0 cm) according to RECISTv1.1 criteria, which is suitable for repeat assessments.
• Tumor size and number requirement: 1 nodule (5cm ≤ size ≤ 7cm); 2-3 nodules, at least 1 nodule \> 3cm, and any nodule ≤ 7cm; 4-5 nodules, any nodule size ≤ 7cm;
• Tumors amenable for initial TACE treatment (Permitted modalities are DEB-TACE or cTACE).
• Tumors were assessed with planning ultrasound and suitable for ablation (by experienced doctor to assess and perform ablation procedure).
• Child-Pugh score class A to B7.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Adequate normal organ and marrow function as defined below, Criteria 'a','b','c' and 'f' allow no transfusions, infusions, or growth factor support administered within 14 days before laboratory test: a. Haemoglobin ≤9.0 g/dL; b. Absolute neutrophil count (ANC) ≥1.0 × 10\^9 /L; c. Platelet count ≥50 × 10\^9/L; d. Serum total bilirubin ≤2 × institutional upper limit of normal (ULN); e. AST (SGOT)/ALT (SGPT) ≤5× ULN; f. Albumin ≥28 g/L; g. International normalized ratio ≤1.6 and prothrombin time ≤16 s; h. Measured creatinine clearance (CL) \>50 mL/min or Calculated creatinine CL\>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min)=Weight (kg) x (140-Age) / (72 x serum creatinine), Females: Creatinine CL (mL/min)=Weight (kg) x (140-Age) ×0.85 / (72 x serum creatinine).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• History or concurrent use of anticancer therapy (local regional therapy and systemic therapy), including investigational products. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. Patients with the recurrence from a radical surgery or ablation are allowed. Evidence for radical surgery or ablation should be provided with enhanced MRI/CT after at least 4 weeks after the treatment and AFP level should also be negative in at least 4 weeks after the radical treatment; Chinese traditional medicine with CFDA approval for anticancer use should be washout for 14 days before enrolment.
• Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or infiltrative-type HCC
• History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
• Ascites requiring invasive intervention (eg, paracentesis) to maintain symptomatic control, within 4 weeks prior to enrolment
• Visible portal vein tumor thrombosis detected on baseline/eligibility imaging
• New York Heart Association Grade ≥2 congestive heart failure; or QTcF value ≥470 ms detected by 12-lead electrocardiogram.
• History of stroke or myocardial infarction or cerebral hemorrhage within 6 months prior to enrolment
• Significant traumatic injury or major surgical procedure (as defined by the Investigator) within 4 weeks prior to enrolment.
• Active GI bleeding, with history of GI bleeding within 6 months, or investigator defined with high risk of haemorrhage for esophageal varices.
• Current use of systemic anticoagulation or anti-platelet drugs.
• History of allogenic organ transplantation.
• Patients weighing ≤30 kg
• Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; Any chronic skin condition that does not require systemic therapy; Patients without active disease in the last 5 years may be included; Patients with celiac disease controlled by diet alone
• History of active primary immunodeficiency
• History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first day of study treatment and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer without evidence of disease; Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

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: Professor

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 18, 2020
• Study Start: July 1, 2021
• Primary Completion: June 1, 2025
• Study Completion: October 1, 2025
• Last Updated: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share