Study of Oligo-Fucoidan in Advanced Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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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 metastatic colorectal cancer. The previous study results demonstrate the advantages of Oligo-Fucoidan in improving the disease control rate. The previous study might provide insights into the development of cancer treatments, particularly in the combination of natural or herbal products with chemotarget agents.

Detailed Description
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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 metastatic colorectal cancer. The previous study results demonstrate the advantages of Oligo-Fucoidan in improving the disease control rate. The previous study might provide insights into the development of cancer treatments, particularly in the combination of natural or herbal products with chemotarget agents.

Official Title
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Study of Oligo-Fucoidan in Advanced Hepatocellular Carcinoma (HCC)

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Dietary Supplement: Oligo Fucoidan
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years; ECOG PS 0-2; Histologically or cytologically documented unresectable HCC; Measurable disease by RECIST criteria; Previous local therapy completed > 6 weeks; Any acute toxicity (CTC-AE) < grade 1; 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 ≥ 3,000/µl; ANC ≥ 1,500/µl; Platelets ≥ 60,000/µl; Hb ≥ 8.5 g/dl; Creatinine ≤ 1.5 x ULN; AND Amylase and lipase < 1.5 x ULN Exclusion Criteria: Metastatic tumors; Prior or concomitant systemic anti-cancer treatment for HCC, including: Systemic chemotherapy (TACE is allowed) Immunotherapy Farnesyltransferase inhibitors VEGF/VEGFR- inhibitors or other anti-angiogenesis agents 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment & Oligo Fucoidan<br>4.4 g Oligo Fucoidan powder by six months, BID | Dietary Supplement: Oligo Fucoidan<br>* 4.4 g oligo fucoidan powder, oral, BID<br>|
| Placebo Comparator: Treatment & Placebo<br>4.4 g Placebo powder by six months, BID | Dietary Supplement: Placebo<br>* 4.4 g placebo powder, oral, BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Disease Control Rate will be evaluated by RECIST version 1.1 | from Day 1 to end of treatment (4th visit, month 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective Response Rate will be evaluated using measurements according to RECISTversion 1.1 | Screening (baseline), complete of Treatment Phase(month 6), and 2 months, 6 months, 12 months and 18 months post-treatment follow up | 
| Overall Survival Rate | Overall Survival Rate will be evaluated using measurements according to RECIST version 1.1 | Screening (baseline), complete of Treatment Phase(month 6), and 2 months, 6 months, 12 months and 18 months post-treatment follow up | 
| Progression Free Survival | Progression Free Survival will be evaluated using measurements according to RECIST version 1.1 | Screening (baseline), complete of Treatment Phase(month 6), and 2 months, 6 months, 12 months and 18 months post-treatment follow up | 
| Quality of Life (QoL) | Quality of Life will be evaluated by questionnaire based on EORTC-QLQ30, specific questions evaluated by scores from 1 (not at all), 2 (a little), 3 (quite a bit), 4 (very much); overall healthy and quality of life will be evalauted by scores from 1 (very poor) to 7 (excellent) | 1st visit to 4th visit (from day 1 to month 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligo Fucoidan