Adjuvant Chemotherapy Combined With Huaier Granule for Treating High-risk Stage II, Stage III Colorectal Cancer

A randomized, paralleled control clinical study investigating Huaier Granule for prevention of recurrence and metastasis of colorectal cancer after radical surgery, to evaluate the efficacy and safety.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Huaier Granule; Drug: Oxaliplatin; Drug: Calcium folinate; Drug: 5-fluorouracil

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • Sixth Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subjects volunteer to sign the informed consent
• Aged: 18 to 75 years old
• Colorectal cancer (AJCC-TNM, high-risk Stage II and Stage III)
• The diagnosis and colorectal cancer has been confirmed by pathological examination after radical surgery
• The liver and kidney function satisfies the following conditions within 15 days after surgery (excluding day 15): aspartate aminotransferase (AST), glutamic-oxalacetic transaminase (ALT), alkaline phosphatase (ALP)< 2 upper limit of normal (ULN), total bilirubin ≤ 1.5 ULN, serum creatinine < 1.5 ULN; normal coagulation function
• Other laboratory tests meet the following requirements within 15 days after surgery (excluding day 15): white blood cells count ≥ 3.0×109/L, absolute neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L
• ECOG：0-2 points
• No other previous history of malignancy.

Exclusion Criteria:

• Multiple primary cancer
• Not recover from the colorectal surgery
• Presence of organ, bone, or skin metastases
• Pregnant or lactating women
• Those with active bleeding due to various reasons
• Those with HIV infection or AIDS-associated diseases
• Those with severe acute and chronic diseases
• Those with severe diabetes
• Those with serious infectious diseases
• Those who can not take drugs by oral route
• Drug abusers or those with psychological or mental diseases that may interfere with study compliance
• Conditions that are considered not suitable for this study investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mFOLFOX6 + Huaier Granule; Twelve cycles of mFOLFOX6 (oxaliplatin, 85 mg/m²; calcium folinate, 400 mg/m²; 5-fluorouracil, 2800 mg/m²). Patients will be treated with chemotherapy every 2 weeks (+/- 2 days ). Huaier Granule will be administrated from the first cycle of chemotherapy until 48 weeks after surgery or until study termination. Huaier Granule is continuously taken three times per day, 20g per time.	Drug: Huaier Granule; Huaier Granule is continuously taken three times per day, 20g per time.; Other Names: Huaier; Drug: Oxaliplatin; 85 mg/m², ivdrip, D1; Drug: Calcium folinate; Calcium folinate 400 mg/m², ivdrip, D1; or calcium levofolinate, 200 mg/m², ivdrip, D1; Other Names: Calcium levofolinate; Drug: 5-fluorouracil; 400 mg/m², iv, D1; and 2400mg/m², civ, 48h
Active Comparator: mFOLFOX6; Twelve cycles of mFOLFOX6 (oxaliplatin, 85 mg/m²; calcium folinate, 400 mg/m²; 5-fluorouracil, 2800 mg/m²). Patients will be treated with chemotherapy every 2 weeks (+/- 2 days ).	Drug: Oxaliplatin; 85 mg/m², ivdrip, D1; Drug: Calcium folinate; Calcium folinate 400 mg/m², ivdrip, D1; or calcium levofolinate, 200 mg/m², ivdrip, D1; Other Names: Calcium levofolinate; Drug: 5-fluorouracil; 400 mg/m², iv, D1; and 2400mg/m², civ, 48h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	DFS was defined as the date of definitive surgery until the date of recurrence, metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS was defined as the date of definitive surgery until the date of death or the last follow-up.	5 years
Relapse-free survival (RFS)	RFS was defined as the date of definitive surgery until the date of recurrence or death from any cause.	5 years
Metastasis-free survival (MFS)	MFS was defined as the date of definitive surgery until the date of metastasis or death from any cause.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effects of Huaier Granule on adverse events of adjuvant chemotherapy.	The adverse events were evaluated every 2 weeks; Eastern Cooperative Oncology Group(ECOG) scores, imaging assessment and related biochemical indicators.	6 months

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Collaborators: Qidong Gaitianli Medicines Co., Ltd
• Investigators: Principal Investigator: Xiaojian Wu, Ph.D., Sixth Affiliated Hospital, Sun Yat-sen University

Publications and helpful links

General Publications

• Zhang N, Kong X, Yan S, Yuan C, Yang Q. Huaier aqueous extract inhibits proliferation of breast cancer cells by inducing apoptosis. Cancer Sci. 2010 Nov;101(11):2375-83. doi: 10.1111/j.1349-7006.2010.01680.x.
• Wang X, Zhang N, Huo Q, Yang Q. Anti-angiogenic and antitumor activities of Huaier aqueous extract. Oncol Rep. 2012 Oct;28(4):1167-75. doi: 10.3892/or.2012.1961. Epub 2012 Aug 8.
• Zhang T, Wang K, Zhang J, Wang X, Chen Z, Ni C, Qiu F, Huang J. Huaier aqueous extract inhibits colorectal cancer stem cell growth partially via downregulation of the Wnt/beta-catenin pathway. Oncol Lett. 2013 Apr;5(4):1171-1176. doi: 10.3892/ol.2013.1145. Epub 2013 Jan 21.
• Wang X, Zhang N, Huo Q, Sun M, Dong L, Zhang Y, Xu G, Yang Q. Huaier aqueous extract inhibits stem-like characteristics of MCF7 breast cancer cells via inactivation of hedgehog pathway. Tumour Biol. 2014 Nov;35(11):10805-13. doi: 10.1007/s13277-014-2390-2. Epub 2014 Jul 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Estimate): June 8, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Efficacy and safety; Huaier Granule; After radical surgery; Prevention of recurrence and metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin; Calcium, Dietary
• Other Study ID Numbers: zsly Huaier-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The investigators would like to share the data to the Participating units.