Clinical Trials /

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

NCT04517227

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: The Combination Therapy of TACE and Ablation With Durvalumab in Hepatocellular Carcinoma at Intermediate Stage (TAD)
  • Official Title: A Single-Arm Open-Label Pilot Study of Combination Therapy of TACE and Ablation With Durvalumab in A Selected Hepatocellular Carcinoma Population at Intermediate Stage

Clinical Trial IDs

  • ORG STUDY ID: ESR-19-20285
  • NCT ID: NCT04517227

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
DurvalumabIMFINZIsingle arm

Purpose

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.

Detailed Description

      Approximately 30 patients will be enrolled and receive the following treatments:

      TACE (day 1, up to twice. TACE interval will be 4~6 weeks) → Ablation (4 weeks after the last
      TACE, up to twice. Ablation interval will be 4~6 weeks) → Durvalumab (at least 1 week after
      the last ablation, 1500 mg Q4W, until mRECIST criteria defined radiological progression or
      other discontinuation criteria were met, but no more than 1 year).
    

Trial Arms

NameTypeDescriptionInterventions
single armExperimentalAll patients enrolled with receive the sequential therapy of TACE, ablation and durvalumab.
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and TB testing in line with
             local practice).

          -  Uncontrolled Hepatitis B (HBV DNA >2000 IU/mL); Patients co-infected with HBV and HCV
             (characterized by detectable HCV RNA, together with positive HBsAg or detectable HBV
             DNA according to local laboratory standards). Anti-viral therapy is recommended
             following the local guidelines. Patients with a non-viral etiology are allowed.

          -  Current or prior use of immunosuppressive medication within 14 days before enrolment.
             The following are exceptions to this criterion:a. Intranasal, inhaled, topical
             steroids, or local steroid injections (e.g., intra articular injection);b. Systemic
             corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its
             equivalent;c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
             premedication, TACE procedure)

          -  Uncontrolled intercurrent illness, including but not limited to, unstable angina
             pectoris, 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 leptomeningeal carcinomatosis.

          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
             criteria.

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients.

          -  Receipt of live attenuated vaccine within 30 days prior to the enrolment. Note:
             Patients, if enrolled, should not receive live vaccine until 30 days after the last
             dose of durvalumab.

          -  Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of durvalumab.

          -  Judgment by the Investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions, and
             requirements

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:From date of the first treatment until 90 days after the last treatment, assessed up to 21 months
Safety Issue:
Description:safety

Secondary Outcome Measures

Measure:Progression-free survival (mRECIST) by IRRC
Time Frame: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
Safety Issue:
Description:efficacy
Measure:Time to progress (mRECIST) by IRRC
Time Frame:From date of the first treatment until the date of first documented progression, assessed up to 36 months
Safety Issue:
Description:efficacy
Measure:PFS rate at 12 months (mRECIST) by IRRC
Time Frame: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
Safety Issue:
Description:efficacy
Measure:PFS rate at 24 months (mRECIST) by IRRC
Time Frame: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
Safety Issue:
Description:efficacy
Measure:Overall survival
Time Frame:From date of the first treatment to the date of death, assessed up to 36 months
Safety Issue:
Description:efficacy

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fudan University

Last Updated

August 18, 2020