A Trial of MB-6 for Reduction of Neutropenia Induced by Chemotherapy in Patients With Stage III Colorectal Cancer.

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled multi-center phaseⅢstudy to evaluate efficacy and safety of oxaliplatin-based chemotherapy plus MB-6(320 mg/capsule, 6 capsules tid) in patients with stage 3 colorectal cancer who underwent surgical excision of their primary tumor.

Detailed Description
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The investigational new drug, MB-6, in the proposed clinical trial is to be used as an adjuvant therapy for metastatic colorectal cancer patients. All of six extracts have been used in human with a long history, and many literatures reported the medicinal use either individually or as ingredients of formulations. MB-6 may provide its therapeutic benefits via inhibition of tumor induction or enhancing the efficacy of chemotherapy in colorectal cancer.

Official Title
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The Purpose of This Study is to Evaluate the Effectiveness of MB-6 as Adjuvant Therapy in Reducing Neutropenia When Given Oxaliplatin-based Chemotherapy in Patients With Stage 3 Colorectal Cancer Previously Treated With Surgery.

Conditions
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Stage III Colorectal Cancer, Neutropenia

Intervention / Treatment
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* Drug: MB-6
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women 20 years of age or older. Histologically or cytologically confirmed stage 3 colorectal adenocarcinoma. Complete resection of the primary tumor without gross or microscopic evidence of residual disease. No more than 8 weeks have elapsed from the time of surgery and have recovered from the effects. Eastern Cooperative Oncology Group Performance Status (ECOG PS) < 2 at the time of screening. Hematological function: ANC≥1500/mm3, Hemoglobin ≥9.0 g/dL, Platelet count ≥100000/mm3. Kidney function:Serum creatinine <2 mg/dL. Liver function: AST ≤3 times ULN, ALT ≤3 times ULN, Total Bilirubin ≤2 times ULN. Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines. Men and women of childbearing potential must agree to employ adequate contraception during the study period. Exclusion Criteria: History of second primary malignancies except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix. Systemic chemotherapy, immune therapy or experimental or approved antibodies/proteins (e.g. bevacizumab) administered after surgery and prior to randomization. Concurrent treatment with any other anticancer therapy. Radiotherapy ≤14 days prior to randomization. Any unresolved toxicity > CTC (Common Toxicity Criteria) grade 1 from previous anti-cancer therapy (including radiotherapy) except haematological toxicity and alopecia. Patients with congestive heart failure, epilepsy, or other significant medical conditions as judged by the investigator. Contraindications to FOLFOX chemotherapy: peripheral neuropathy NCI CTC >1, liver failure, uncontrolled coronary heart disease, myocardial infarction within the previous 6 months before randomization. Patient of child-bearing potential is evidently pregnant or is breast feeding.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MB-6+FOLFOX chemotherapy<br>MB-6, 6 capsules tid be taken with meals plus FOLFOX chemotherapy, will be given for 18 weeks | Drug: MB-6<br>* 6# TID with meal<br>* Other names: Folinic acid; Fluorouracil ; Oxaliplatin;|
| Placebo+FOLFOX chemotherapy<br>Placebo, 6 capsules tid be taken with meals plus FOLFOX chemotherapy, will be given for 18 weeks | Drug: Placebo<br>* 6# TID with meal<br>* Other names: Folinic acid; Fluorouracil ; Oxaliplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the incidence of grade 4 neutropenia during the chemotherapy period, defined as an absolute neutrophil count (ANC) <500/mm3. | The primary endpoint is the incidence of grade 4 neutropenia during the chemotherapy, defined as an absolute neutrophil count (ANC)<500/mm3 | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first Grade 4 Neutropenia | To determine the time interval from randomization to the first episode of grade 4 Neutropenia. The analyses for incidence of study event will be conducted using logistic regression model method to adjust for gender and the regimen of chemotherapy (e.g., FOLFOX4 or FOLFOX6). | 18 weeks | 
| Incidence of Febrile Neutropenia | The febrile neutropenia is defined as an ANC <1000/mm3 and a single temperature ≥38.3 degree of C or a sustained temperature of ≥38.0 degree C for more than one hour. | 18 weeks | 
| Incidence of Grade 3 or 4 Neutropenia | The grade 3 or 4 neutropenia during the chemotherapy period is defined as an absolute neutrophil count (ANC) <1000/mm3. | 18 weeks | 
| Change in Serum Creatinine level | Any change in Serum Creatinine level during the chemotherapy period | 18 weeks | 
| Health-Related Quality of Life (HRQoL) - QLQ-C30 | Health-Related Quality of Life (HRQoL) - QLQ-C30 should be completed at baseline, day 71 and end of study. | 18 weeks | 
| Quality of Life -VAS on Fatigue, Constipation, Appetite | Quality of Life -VAS on Fatigue, Constipation, Appetite will be assessed by patients every two weeks until end of study. | 18 weeks | 
| Compliance with Chemotherapy | The compliance with chemotherapy will be summarized by descriptive statistic and listed by each cycle and overall period. | 18 weeks | 
| Increase in Body Weight | Any increased body weight during the chemotherapy period. | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage III Colorectal Cancer, Grade 4 Neutropenia, MB-6