Chemotherapy-induced Neutropenia, Colorectal Cancer
Conditions
Brief summary
The primary objective of this study is to assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity in colorectal cancer patients who received oxaliplatin-based adjuvant chemotherapy.
Detailed description
Oxaliplatin is a key agent in the treatment of colorectal cancer. However, peripheral neuropathy markedly limits the use of oxaliplatin. Many drugs have been tried to decrease the development of oxaliplatin induced peripheral neurotoxicity, however, the results remain disappointing. This multi-center, randomized, placebo-controlled trial was performed to assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity in colorectal cancer patients who received oxaliplatin-based adjuvant chemotherapy.
Interventions
DRUGGM1
GM1 will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4), and the dosages of GM1 for patients who receive mFOLFOX6 or XELOX are 80mg or 120mg per day.
DRUGplacebo
Placebo will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4), and the dosages of placebo for patients who receive mFOLFOX6 or XELOX are 80mg or 120mg per day.
DRUGmFOLFOX6 or XELOX
mFOLFOX6: Patients will receive mFOLFOX6 every 14 days, Oxaliplatin 85mg/m2 IV over 3 hours on Day1; Calcium Folinate IV over 2h on Day 1(Leucovorin 200mg/m2 or CF 400 mg/m2); 5-Fluorouracil 400mg/m2 IV on Day1; followed by 5-Fluorouracil 2.4g/m2 for 46 hours continuous infusion on Day1. XELOX: Patients will receive XELOX every 21 days, Oxaliplatin 130mg/m2 IV over 3 hours on Day1;followed by Capecitabine 1000mg/m2 oral twice daily for 14 days. The optimum chemotherapy regimen is at the discretion of the investigators based on the condition of each patient.
Sponsors
Yuhong Li
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-75 years old, male or female * Histologically confirmed diagnosis of colorectal adenocarcinoma with a phase II or III disease, within 2 months from radical resection, and intends to receive 6 months of adjuvant chemotherapy with mFOLOFX6 or XELOX, without adjuvant radiation indications * No prior any level of peripheral nerve system disease * Patients have not received any other possible neurotoxic-reaction-causing drugs (such as oxaliplatin, cisplatin and paclitaxel drugs etc) * With the capability to accurately record the occurrence and severity of neurotoxicity by questionnaire * With normal functions of major organs * No contraindication to chemotherapy * Life expectancy ≥ 3 months * Patients have provided a signed Informed Consent Form
Exclusion criteria
* Patients who received radical resection, but are expected not be able to complete 6 months of adjuvant chemotherapy * Patients who receive palliative chemotherapy * Patients who need adjuvant or palliative radiotherapy during chemotherapy * Be allergic to GM1 * Hereditary abnormal metabolism of glucose and lipid * Doctors believe that patients are not suitable for receiving GM1 treatment * With confirmed history of neurological or psychiatric disorders, including epilepsy and dementia * With concomitant diseases that will seriously harm the patients' safety or impact the completion of the study * Patients (male or female) have fertility possibility but not willing or not to take effective contraceptive measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rates of grade 2 or more chronic cumulative neurotoxicity of both arms | 9 months | measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0, with standardized questions regarding neurotoxic symptoms and examples of answers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| rates of chronic cumulative neurotoxicity of both arms | 9 months | measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 |
| time to grade 2 or more neurotoxicity of both arms | 9 months | — |
| rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms | 9 months | — |
| rates and grades of adverse reactions of both arms | 6 months | — |
| rates of 3 year disease free survival of both arms | 3 years | — |
| rates of acute neurotoxicity of both arms | 6 months | measured by a numerical analog scale ranging from 0 to 10 that addressed sensitivity touching cold items, discomfort swallowing cold items, throat discomfort, and muscle cramps |
Other
| Measure | Time frame |
|---|---|
| change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms | 6 months |
| genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity | 6 months |
Countries
China
Outcome results
None listed