Monosialotetrahexosylganglioside Sodium Injection for Prevention Neurotoxicity of mFOLFOX 6 in mCRC

The Safety and Effect of Monosialotetrahexosylganglioside Sodium Injection for Prevention Neurotoxicity of mFOLFOX6 as First-line Chemotherapy for Advanced Colorectal Cancer

The morbidity of colorectal cancer(CRC) is 10%～15% in China.mFolfox6 has become one of the standard regimes for metastatic colorectal cancer (mCRC). Neutropenia and oxaliplatin-induced neurotoxicity are the most common adverse effects which even result in discontinue of chemotherapy, especially for patients suffered from heavily acute neurotoxicity. Monosialotetrahexosylganglioside is a component of membrane of nerve cells. Previous phase II clinical trial showed, it can reduce oxaliplatin-induced neurotoxicity(OIN). But it did not certificated by phase III trial. Investigators designed the phase III trial to investigate the effect and safety of monosialotetrahexosylganglioside Sodium Injection for prevention OIN at colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: monosialotetrahexosylganglioside Sodium; Other: placebo

Detailed Description

it is a placebo controlled phase III trial. investigators plan to enroll 240 patients with 1:1 to A arm and B arm

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: YI BA, MD PHD; Phone Number: +8602223340123-1051; Email: zhoubaling123@163.com
      • Principal Investigator: yi ba, MD PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients shall have normal organic function such as liver function, Cardiac function and renal function;
2. age >18 years old;
3. diagnosis mCRC with histology;
4. Did not received first-line chemotherapy
5. Karnofsky Performance scores >70 scores
6. should have target lesions or non-target lesions
7. For patients received oxaliplatin before, the residual neurotoxicity should less than grade 2
8. For diabetes without neuropathy, blood glucose before meal should less than 8mmol/L and HBA1C<7.0%
9. Patients should be expected to live no shorter than 3 months

Exclusion Criteria:

1. patients who is receiving chemotherapy;
2. WBC<4.0×109/L，ANC<1.5×109/L,PLT<100×109/L，Hb<90g/L,TBIL>1.5Limitation;BUN）>1.5Limitation；Cr）>1.5Limitation；ALT or AST>2.5Limitation（without liver metastasis）；ALT or AST）>5Limitation（with liver metastasis）;
3. heart dysfunction;
4. brain metastasis;
5. peripheral nervous system or central nervous system abnormal including diabetes mellitus patients with neuropathy;
6. patients who received Glutathione, acetylcysteine, calcium / magnesium, amifostine, carbamazepine, B vitamins, vitamin E within 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: monosialotetrahexosylganglioside Sodium; arm A: monosialotetrahexosylganglioside Sodium Injection, 40mg,one hour before chemotherapy(mFOLFOX6), every two weeks until tumor progress or patients become intolerant	Drug: monosialotetrahexosylganglioside Sodium; it is a component extract from pig's brain,shenjie is the brand name; Other Names: shenjie
Placebo Comparator: placebo; arm B: equal saline as placebo ,one hour before chemotherapy(mFOLFOX6) every two weeks until tumor progress or intolerant	Other: placebo; saline of the same appearance as monosialotetrahexosylganglioside Sodium; Other Names: saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of neurotoxicity including acute neurotoxicity and accumulating neurotoxicity	Acute neurotoxicity will be assessed the first day of oxaliplatin at every cycle given;accumulating neurotoxicity will be assessed every two weeks from the second day of first cycle until the patients out of the study. The accumulating neurotoxicity will be assessed every four weeks for 12 months or one week before second-line chemotherapy	From the first day of chemotherapy to 12 months after study or until one week before the patients receive second-line chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Investigators assess the effect every six weeks and objective response is recorded as complete response,partial response or stable disease according to Recist 1.1	Eevery 6 weeks, up to 24 months
Progress Free Survival	From date of randomization until the date of first documented progression	investigators assess the effect of chemotherapy every 6 weeks ,up to 24 months
overall Survival	the patients will be followed one month after progression ,then every 3 months,up to 100 months	From date of randomization until the date of death from any cause, assessed up to 100 months
quality of life	we use sf-36 to evaluated the quality of life	evaluate 1 week before chemotherapy and every 6 weeks of study. And evaluate within 4 weeks after the patients out of the study

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Study Director: Yi Ba, MD.PHD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: November 24, 2013
• First Submitted That Met QC Criteria: December 26, 2013
• First Posted (Estimate): December 31, 2013

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 24, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: neurotoxicity; metastatic colorectal cancer; mFOLFOX6; monosialotetrahexosylganglioside Sodium Injection
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Poisoning; Colorectal Neoplasms; Neurotoxicity Syndromes
• Other Study ID Numbers: 20131123; E2013109A (Other Identifier: TianjinCIH)