Clinical trial NCT02729506: Transarterial Radioembolization Versus Chemoembolization for the Treatment of Hepatocellular Carcinoma
Official title: Transarterial Radioembolization Versus Chemoembolization for the Treatment of Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
transarterial radioembolization
chemoembolization chemoembolization
clinical trial
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
First posted: 2016-04-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hepatocellular Carcinoma (HCC) is a primary liver cancer. It is the 6th most common malignancy and the 3rd killers of all tumors worldwide with an incidence of 626,000 new patients a year. The intermediate stage of HCC is controlled by radiological interventions such as Transarterial Chemoembolization (TACE) or Radioembolization. Although 90Y radioembolization is increasingly being used in clinical practice, there is no high quality clinical evidence to justify this. To date, no prospective studies have been performed comparing both treatment modalities (TACE vs 90Y) in a randomized setting. This randomized controlled trial is designed to prospectively compare TACE and 90Y for treatment of patients with unresectable (BCLC intermediate stage) HCC. This will be done by recruiting 75 patients in each arm from. Investigators will compare between the two groups the time to progression (TTP) as the primary outcome and also examine time to local progression (TLP) as well as other factors like overall survival, response to therapy, toxicities and adverse events, quality of life and treatment-related costs.

Detailed description: Study Rationale:

Although 90Y increasingly used in clinical practice, there is no high quality clinical evidence to justify this. Most of the comparison studies are retrospective. Three studies compared TACE with 90Y retrospectively. The first was by Kooby et al in which patients treated with TACE were retrospectively compared to those treated with 90Y suggested that both treatment modalities have similar effectiveness and safety profiles in patients with unresectable HCC. Earlier Carr et al carried out a similar retrospective analysis and concluded that Chemoembolization or Radioembolization appeared to be equivalent regional therapies for patients with unresectable, non-metastatic HCC. More recently Salem et al retrospectively compared 122 HCC patients who received chemo-embolization with 123 patients who received Radioembolization and concluded both patient groups had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemo-embolization.

A study on down-staging of HCC beyond Milan criteria compare 90Y with TACE of and concluded that 90Y outperforms TACE for down-staging HCC to within transplant criteria.

TACE-DEB is the standardized form TACE with better efficacy and safety profile and will be ideal to use to define the position of 90Y in the of locoregional treatment of HCC.

To date, no prospective studies have been performed comparing both treatment modalities in a randomized setting. This randomized controlled trial is designed to prospectively compare TACE and 90Y for treatment of patients with unresectable (BCLC intermediate stage) HCC.

Known Potential Benefits:

Chemo-embolization is the standard treatment for intermediate HCC with known efficacy and predicted toxicity. The arrival of TAC-DEBs made TACE more efficient, less toxic and more standardized. Y90 Radioembolization is of known efficacy and minimal toxicity base on cohort studies. Head to head comparison has never been conducted.

Eligibility criteria: Inclusion Criteria:

* Patients with measurable, locally advanced HCC those are not suitable to have or have failed potentially curable intervention (Radio frequency ablation for small tumor, resection or transplantation).
* The diagnosis of HCC should be established either by cyto/histology; or, by characteristic imaging studies in patients with cirrhosis of the liver and/or chronic viral hepatitis B or C infection.
* Patients must not be less than 18 and not more than 80 and can be either gender.
* Patients must have a performance status of ECOG score equal to or less than 2.
* Child-Pugh's A or Early B, score 8 and above (see table)
* Patients must have adequate organ function as evidenced by:

Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelet count ≥50 x 109/L Hg \>9 g/d. AST or ALT ≤5 x ULN Serum creatinine ≤2 x ULN OR creatinine clearance ≥50 mL/min (estimated by Cockcroft Gault or measured) Normal mg and K Bleeding diathesis or on Vit. K therapy.

* Patients must fulfill Child-Pugh's Score
* Life expectancy equal to or more than 12 weeks.
* Signed informed consent.
* Sexually active patients, in conjunction with their partner, must practice birth control during, and for 2 months after therapy.
* Female patients at child-bearing age must have negative pregnancy test.
* No known HIV infection.

Exclusion Criteria:

* Patients with metastases outside the liver.
* Patients with co-morbid condition that will be aggravated by the investigational drug or by the intervention.
* Patients with severe cardiopulmonary diseases (including history of stable, effort-induced or unstable angina pectoris or myocardiac infarction) and other systemic diseases under poor control.
* Patients with active infection.
* Patients with history of psychiatric disorder.
* Patients with concomitant active secondary malignancies, except for surgically cured carcinoma in situ of the cervix and basal or adequately treated squamous cell carcinoma of the skin. Disease-free of malignancies \< 2 years before the study, are not eligible.
* Clinically significant third space fluid accumulation (i.e., ascites requiring paracentesis despite use of diuretics) or pleural effusion that either requires thoracocentesis or is associated with shortness of breath
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.
* Concurrent usage of hormonal or chemotherapeutic agents.
* Patients who received surgery, radiotherapy except to bone, chemotherapy, immunotherapy, or other investigational drug within 4 weeks before initiating study are not eligible.
* Patients who are pregnant, breast-feeding or not using appropriate birth control during the course of the study.
* Patients with partner of child bearing age who are not willing to use appropriate contraceptives during and 8 week after therapy.
* Non compliance.
* Unwilling to disclose medical information.

Primary outcomes:
measure: Time to Progression (TTP) is the primary outcome.
timeFrame: 12 month
Secondary outcomes:
measure: Time to Local Progression (TLP)
timeFrame: 12 month
measure: Overall survival
timeFrame: 12 month
measure: Overall response to therapy according to mRECIST
timeFrame: 12 month
measure: Toxicities and adverse events
timeFrame: 12 month
measure: Quality of life
timeFrame: 12 month
measure: Treatment-related costs, in terms of cost of therapy and number of hospitalization days.
timeFrame: 12 month
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specilist Hopsital & Researchc Center
Study officials:
affiliation: King Faisal Specilaist Hopsital & Research Center
name: Mohamed I Al Sebayel, Prof
role: PRINCIPAL_INVESTIGATOR
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