Effect of GM1 in Prevention of Taxanes Induced Neurotoxicity in Operable Breast Cancer

NCT02468739 | Completed Phase 3 DMC

• 1 other identifier: SYSUCC-013
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Taxane plays a key role in the treatment of breast cancer and taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect leading to treatment discontinuation. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. However, the effects of GM1 on TIPN in breast cancer patients remains unknown. Purpose: This randomized phase III trial is designed to evaluate the potential effects of GM1 for preventing TIPN in breast cancer patients.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale between groups at 2 weeks after the 4-cycle chemotherapy

  The primary endpoint was assessed using the Functional Assessment of Cancer Treatment, Gynecologic Oncology Group Neurotoxicity (FACT -Ntx) subscale at 2 weeks after completion of 4-cycles of taxane-based chemotherapy. FACT-Ntx subscales contains 11 items including numbness, tingling, and discomfort in the hands or feet; difficulty hearing or tinnitus; joint pain or muscle cramps; weakness or fatigue; or trouble walking, buttoning buttons, or feeling small shapes when placed in the hand; feeling pain or hard to breath when exposed to low temperature. Each Items is scored from 0 to 4 with a total score of 44; higher scores indicate better performance. A 5-point difference in the FACT-Ntx subscale scores between groups is considered clinically meaningful. The FACT-Ntx subscales assessments were performed at 2 weeks after each course of chemotherapy. Additional long-term assessments were performed at 3 months, 6 months and 1 year after the end of chemotherapy.

  Day 1 of Week 1 to 1 year after the last course of chemotherapy

Secondary Outcomes (2)

• neurotoxicity evaluated by NCI-CTCAE version 4.0 grading scale

  1 monthDay 1 of Week 1 to 1 year after the last course of chemotherapy

• neurotoxicity evaluated by the Eastern Cooperative Oncology Group neuropathy scale (ENS) subscales of sensory neuropathy, motor neurotoxicity, and neurogenic constipation.

  Day 1 of Week 1 to 1 year after the last course of chemotherapy

Study Arms (2)

Ganglioside-monosialic acid arm

EXPERIMENTAL

Patients will receive treatment of adjuvant chemotherapy. Ganglioside-monosialic acid(GM1, 80mg per day) will be given at 1 day before the start of chemotherapy for three days (Day -1, 1 and 2). Chemotherapy regimens: Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by paclitaxel (175 mg/m2 \*4 cycles) after four courses of chemotherapy; Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by docetaxel (75 mg/m2 \*4 cycles) after four course of chemotherapy; Docetaxel (75 mg/m2 q21d) combined with cyclophosphamide (600 mg/m2) for four courses. The first day (D1) of each cycle is treated with taxane-based chemotherapy. 14-21 days are usually as one cycle. The methods of pretreatment and hydration shall be decided by the physicians.

Drug: Ganglioside-monosialic acid

placebo arm

PLACEBO COMPARATOR

Patients will receive treatment of adjuvant chemotherapy. Placebo will be given at 1 day before the start of chemotherapy for three days (Day -1, 1 and 2). Chemotherapy regimens: Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by paclitaxel (175 mg/m2 \*4 cycles) after four courses of chemotherapy; Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by docetaxel (75 mg/m2 \*4 cycles) after four course of chemotherapy; Docetaxel (75 mg/m2 q21d) combined with cyclophosphamide (600 mg/m2) for four courses. The first day (D1) of each cycle is treated with taxane-based chemotherapy. 14-21 days are usually as one cycle. The methods of pretreatment and hydration shall be decided by the physicians.

Drug: placebo

Interventions

Ganglioside-monosialic acid DRUG

Ganglioside-monosialic sodium is added into to 250 ml of 0.9% sodium chloride injection, which is given once a day via intravenous drip infusion for 3 days. The first dose is given at 1 day before the start of the chemotherapy.(day -1, day 1 and day2). The dosages of GM1 are 80mg per day.

Also known as: GM1

Ganglioside-monosialic acid arm

placebo DRUG

Placebo is added into to 250 ml of 0.9% sodium chloride injection, which is given once a day via intravenous drip infusion for 3 days. The first dose is given at 1 day before the start of the chemotherapy.(day -1, day 1 and day2).

placebo arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• There are any toxicity events of peripheral nervous system before enrollment, including: FACT-Ntx subscale score \< 44;≥ Grade 1 peripheral toxicity according to CTCAE Version 4.0 rating scale;≥ Grade 1 peripheral toxicity according to ENS rating scale;All other pathological symptoms or diseases might affect the evaluation of adverse neurotoxic effects
• Patients having received other drug treatments might cause similar adverse neurotoxic effects within 4 weeks prior to the treatment of this protocol, or receive concurrent neurotoxic drugs. Including: Taxanes or analogues; Vinca alkaloids or analogues; Platinums or analogues; Cytarabine, thalidomide, bortezomib, or procarbazine; Other drugs or treatments might cause peripheral neurotoxicity
• Patients in poor general conditions, with KPS (Karnofsky performance status) scores \< 80;
• Pregnant or lactating women；
• Patients (female) having the possibility of fertility but unwilling or not taking effective contraceptive measures
• Patients also having other neurological abnormalities who cannot accurately record the occurrence and severity of neurotoxicity;
• Patients known allergy to trial drugs or excipient compositions of these products;
• Patients with inherited glucose and lipid metabolism abnormalities (gangliosidosis such as amaurotic family idiocy and retinopathy);
• Patients not suitable for treatment of ganglioside;
• Active infection (depending on the judgment of investigators);
• Patients with serious concurrent diseases might harmful to safety and interfere the scheduled treatment or concomitant diseases might affect the completion of the study, depending on the judgment of investigators.
• Patients with a history of definite neurological or dysphrenia, including epilepsy or dementia.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Zhong-Yu Yuan, M.D.

  Sun Yat-sen University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: June 11, 2015
• Study Start: May 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 4, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)