After interim analysis, we planned to recruit 100 participants. However, due to COVID-19 challenges, statistician advised each group needs at least 30 samples (Gay, 1992). The sponsor and team decided to terminate the trial early for valid data.

A randomized, double-blind, controlled trial was conducted evaluating the efficacy of Oligo-Fucoidan with the molecular weight ranged from 500 to 800 Da. as a supplemental therapy in patients with advanced hepatocellular carcinoma. The previous study results demonstrate the advantages of Oligo-Fucoidan in improving the disease control rate in metastatic colorectal cancer. The previous study might provide insights into the development of cancer treatments, particularly in the combination of natural or herbal products with chemotarget agents.

Oligo-Fucoidan, a heparin-like molecule with high percentages of L-fucose and sulfated ester groups and low percentages of D-xylose, D-galactose, D-mannose, and glucuronic acid, was present in the cell wall matrix of brown seaweed. Brown seaweed Oligo-Fucoidan was reported to demonstrate various biological activities such as antioxidant, anti-inflammatory, antiproliferative, and proapoptotic activities. Oligo-Fucoidan was also revealed to inhibit the growth of breast and lung cancers in animal models. Oligo-Fucoidan treatment induces the degradation of transforming growth factor (TGF)-β receptor and the consequent inhibition of the epithelial-mesenchymal transition (EMT) in cancer cells. In addition to these molecular mechanisms, it is imperative to investigate the potential of Oligo-Fucoidan as a miRNA regulator for breast cancer treatment and thus delineate the molecular mechanisms underlying the anticancer effects of Oligo-Fucoidan. A randomized, double-blind, controlled trial was conducted evaluating the efficacy of Oligo-Fucoidan with the molecular weight ranged from 500 to 800 Da. as a supplemental therapy in patients with . advanced hepatocellular carcinoma. The previous study results demonstrate the advantages of Oligo-Fucoidan in improving the disease control rate in metastatic colorectal cancer. The previous study might provide insights into the development of cancer treatments, particularly in the combination of natural or herbal products with chemotarget agents.

Inclusion Criteria:

• Age > 18 years;
• ECOG PS 0-2;
• Histologically or cytologically documented unresectable HCC;
• Measurable disease by RECIST criteria;
• HCC without well control
• Child-Pugh A-B
• Albumin ≥ 2.8 g/dl;
• Serum total bilirubin ≤ 3 mg/dl;
• INR ≤ 2.3 or PT ≤ 6 seconds above control;
• WBC ≥ 2,500/µl;
• ANC ≥ 1,000/µl;
• Platelets ≥ 50,000/µl;
• Hb ≥ 8.5 g/dl;
• Creatinine ≤ 1.5 x ULN; AND

Exclusion Criteria:

• Metastatic tumors;
• Prior or concomitant systemic anti-cancer treatment for HCC, including:
• Systemic chemotherapy (TACE is allowed)
• Investigational anti-cancer agents
• Severe and/or uncontrolled medical conditions:
• Uncontrolled high blood pressure
• History of poor compliance with anti-hypertensive agents
• Active or uncontrolled infection
• Unstable angina
• CHF
• MI or CVA < 6 months
• GI bleeding < 30 days
• Unable to take oral medications
• Severe renal impairment which requires dialysis; proteinuria > grade 2;
• BMT or stem cell rescue < 4 months; organ transplant;
• HIV infection;
• Major surgical procedure, open biopsy, or significant traumatic injury < 4 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 2 weeks;
• Patients taking narrow therapeutic index medications will be monitored closely. These include warfarin, phenytoin, quinidine, carbamazepine, phenobarbital, cyclosporine, and digoxin.