GM1 for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer

Recruiting at 38 trial locations

Overseen By Aishwarya Vijendran

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Paclitaxel

Must not be taking: Duloxetine

Disqualifiers: Fibromyalgia, Stroke, Neurologic disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether GM1 (Monosialotetrahexosylganglioside) can reduce or prevent chemotherapy-induced peripheral neuropathy (CIPN), a nerve condition causing weakness, numbness, and pain, in breast cancer patients receiving paclitaxel. Researchers are assessing the safety, side effects, and optimal dose of GM1, known for its nerve-protective properties. Participants will receive either GM1 or a placebo (inactive treatment) alongside their chemotherapy. Ideal candidates have metastatic breast cancer, experience minimal CIPN symptoms, plan to start paclitaxel, and have not previously used GM1. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use duloxetine or certain therapies like cryotherapy during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GM1, a type of compound, is generally safe for people. Studies have found that GM1 is well-tolerated and can help reduce nerve damage symptoms in conditions like diabetic nerve pain and Parkinson's disease. This suggests it might also be safe for those with nerve pain caused by chemotherapy. Additionally, GM1 may help lessen severe nerve pain in patients with advanced breast cancer when used with other treatments.

While these findings are promising, each person's experience can vary. Participants should discuss any concerns with a healthcare professional before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chemotherapy-induced peripheral neuropathy?

Unlike the standard treatments for chemotherapy-induced peripheral neuropathy, which often involve medications like duloxetine or gabapentin to manage symptoms, GM1 is unique because it directly targets nerve protection and repair. GM1 is a type of ganglioside that can help stabilize cell membranes and promote nerve regeneration, potentially reducing nerve damage caused by chemotherapy drugs like paclitaxel. Researchers are excited about GM1 because it offers a novel approach that goes beyond symptom management by potentially preventing or repairing nerve damage, which could significantly improve the quality of life for patients undergoing chemotherapy.

What evidence suggests that GM1 might be an effective treatment for chemotherapy-induced peripheral neuropathy?

Research shows that a substance called GM1 might help prevent nerve damage caused by chemotherapy. In this trial, one group of participants will receive GM1 with paclitaxel, while another group will receive a placebo with paclitaxel. Previous studies have shown that GM1 is promising in reducing nerve problems for patients undergoing chemotherapy. For example, a review of several studies found that GM1 could effectively prevent chemotherapy-induced peripheral neuropathy, a common side effect of cancer treatment. Another study found that GM1 significantly reduced nerve damage symptoms compared to a placebo. These findings suggest that GM1 might help protect nerves during cancer treatment, especially for patients receiving drugs like paclitaxel. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with metastatic breast cancer who are receiving paclitaxel and have normal liver function, no severe neurological or psychiatric disorders, and can complete questionnaires in English/Spanish. They should not be using certain therapies or drugs like duloxetine, have a recent serious infection, previous GM1 exposure, or plan to use immunotherapy.

Inclusion Criteria

I understand the benefits and risks of participating in this trial.

I can speak and/or read English or Spanish.

I am not planning to receive immunotherapy alongside other treatments.

Exclusion Criteria

N/A

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Early Phase Treatment

Patients receive GM1 intravenously over 1 hour either once every 7 days, or once every 7 days for 3 doses followed by one week off, prior to paclitaxel administration.

6-7 months

Phase II Treatment

Patients are randomized to receive either GM1 or placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival.

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Monosialotetrahexosylganglioside

Trial Overview The trial is testing the safety and optimal dose of GM1 to see if it reduces or prevents numbness and weakness caused by chemotherapy (CIPN) in patients treated with paclitaxel. It includes quality-of-life assessments compared to a placebo.

How Is the Trial Designed?

Group I: Arm I (paclitaxel, GM1) Experimental Treatment 4 Interventions

Patients receive GM1 IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.

Group II: Arm II (paclitaxel, placebo) Placebo Group 4 Interventions

Patients receive placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intracerebroventricular injection of vincristine in rats led to significant motor and reflex impairments, weight loss, and a marked decrease in hippocampal choline acetyltransferase (ChAT) activity, indicating neurotoxic effects due to neuronal death.

Daily administration of GM1 ganglioside effectively prevented the decrease in ChAT activity and improved behavioral outcomes, suggesting it may protect against vincristine-induced neurotoxicity, especially when treatment starts shortly after the vincristine injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GM1 ganglioside counteracts cholinergic and behavioral deficits induced in the rat by intracerebral injection of vincristine. Di Patre, PL., Abbamondi, A., Bartolini, L., et al.[2019]

In a study of 278 colorectal cancer patients, the use of monosialotetrahexosylganglioside (GM1) significantly reduced the incidence of acute and chronic neurotoxicity caused by oxaliplatin, with lower rates of both grade 1-3 and grade 2 acute neurotoxicity in the GM1 group compared to the control group.

Despite the reduction in neurotoxicity, GM1 did not affect the overall efficacy of oxaliplatin treatment, as there were no differences in response rates or survival outcomes between the GM1 and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of monosialotetrahexosylganglioside (GM1) in prevention of oxaliplatin induced neurotoxicity: a retrospective study. Chen, XF., Wang, R., Yin, YM., et al.[2020]

In a meta-analysis of five studies with 868 participants, GM1 did not significantly reduce the incidence of chemotherapy-induced peripheral neuropathy (CIPN) for patients treated with oxaliplatin, indicating limited efficacy in this subgroup.

However, GM1 showed potential in reducing the risk of CIPN in patients receiving taxane-based chemotherapy, suggesting it may be beneficial for this specific group, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis. Wu, S., Bai, X., Guo, C., et al.[2022]

In a study of 126 women treated with taxane-based chemotherapy for breast cancer, 73% reported experiencing chemotherapy-induced peripheral neuropathy (CIPN), which significantly affected their quality of life and physical functioning.

CIPN severity was notably higher in Black or African American women, indicating a need for targeted screening and intervention strategies to address this disparity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice. Simon, NB., Danso, MA., Alberico, TA., et al.[2022]

In a study of 206 early-stage breast cancer patients undergoing taxane-based chemotherapy, the use of GM1 significantly improved neurotoxicity scores compared to a placebo, indicating its effectiveness in reducing taxane-induced peripheral neuropathy (TIPN).

The GM1 treatment group experienced a much lower incidence of grade 1 or higher neurotoxicity, with only 14.3% affected compared to 100% in the placebo group, demonstrating its potential as a protective agent against chemotherapy-related nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial. Su, Y., Huang, J., Wang, S., et al.[2020]

In a study of 488 women receiving docetaxel or paclitaxel, 37.3% of dose-limiting chemotherapy-induced peripheral neuropathy (CIPN) events were attributed to paclitaxel, with a significantly higher incidence (16.1%) compared to docetaxel (2.4%).

Women who experienced dose reductions or treatment discontinuation due to CIPN received significantly less cumulative chemotherapy than planned, indicating that CIPN can impact treatment effectiveness and necessitates further investigation into its implications on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. Speck, RM., Sammel, MD., Farrar, JT., et al.[2022]

Paclitaxel, a chemotherapy drug, commonly causes peripheral neuropathy (PN) in breast cancer patients, with symptoms like painful paresthesias and weakness developing progressively during treatment.

The study found that PN symptoms developed more rapidly in patients receiving paclitaxel alone compared to those receiving it with adriamycin, highlighting the need for neuroprotective strategies in chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral neuropathy due to paclitaxel: study of the temporal relationships between the therapeutic schedule and the clinical quantitative score (QST) and comparison with neurophysiological findings. Augusto, C., Pietro, M., Cinzia, M., et al.[2018]

In a study involving 120 patients with gastrointestinal tumors, the administration of GM1 significantly reduced the severity of oxaliplatin-induced neurotoxicity compared to a control group, indicating its potential as a neuroprotective agent.

Patients receiving GM1 experienced a higher incidence of low-grade neurotoxicity and a lower incidence of high-grade neurotoxicity, suggesting that GM1 effectively mitigates severe side effects without compromising the chemotherapy's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors. Zhu, Y., Yang, J., Jiao, S., et al.[2021]

Chronic sensory neuropathy in chemotherapy patients is influenced by complex interactions between cancer and chemotherapy, which affect neuronal excitability and inflammatory responses, as shown by global transcriptional profiling of dorsal root ganglia.

The study identified Kv3.3 potassium ion channels as a potential contributor to sensory neuron dysfunction, and revealed new behavioral deficits in forelimb placement that were not predicted by previous studies of chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy. Housley, SN., Nardelli, P., Carrasco, DI., et al.[2021]

In a study involving 36 healthy volunteers (12 per dose group), pharmacokinetic parameters of GM1 were assessed at three different doses (100, 200, and 300 mg), showing that higher doses resulted in increased plasma levels of GM1, with the average area under the curve (AUC) rising significantly from 1002 to 3155 micrograms mL-1 h.

GM1 demonstrated low plasma clearance and a mean residence time of about 43 hours across all doses, indicating that it remains in the body for a considerable duration, but it was not detected in urine, suggesting limited renal excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of GM1 ganglioside following parenteral administration. Cornelli, U., Panucci, A., Zingali, G., et al.[2019]

In a study of 196 colorectal cancer patients undergoing oxaliplatin-based chemotherapy, GM1 did not significantly reduce the rate of severe cumulative neurotoxicity compared to placebo, indicating it may not be effective for this purpose.

However, GM1 was associated with a significant reduction in participant-reported acute neurotoxicity symptoms, such as sensitivity to cold and throat discomfort, suggesting it may help alleviate some immediate side effects of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer. Wang, DS., Wang, ZQ., Chen, G., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33163394/

Ganglioside Monosialic Acid Alleviates Peripheral ... Conclusion: Ganglioside monosialic acid potentially decreases severe utidelone plus capecitabine-induced peripheral neuropathy in metastatic ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08884-4

Ganglioside-monosialic acid (GM1) for prevention of ... Preclinical animal models suggested that porcine GM1 could be effective in the prevention and treatment of paclitaxel-induced neuropathy [14].

3. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00437-5/fulltext

TJMUCH-GI-001, a randomised controlled trial The primary endpoint was the relief of neurotoxicity (≥30% improvement), measured by a newly developed patient reported outcome measure (MCIPN) ...

4. withpower.com withpower.com/trial/phase-2-breast-neoplasms-2-2023-b5e05

GM1 for Chemotherapy-Induced Peripheral Neuropathy in ... A meta-analysis found that Ganglioside-monosialic acid (GM1) may be effective in preventing chemotherapy-induced peripheral neuropathy, a common side effect of ...

5. academic.oup.com academic.oup.com/jnci/article/112/1/55/5489913

Effects of Ganglioside-Monosialic Acid in Taxane-Induced ... The treatment with GM1 resulted in a clinically significant reduction in the severity and incidence of TIPN compared with placebo after four ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34727879/

Ganglioside-monosialic acid (GM1) for prevention of ... This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN.

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.524223/full

Ganglioside Monosialic Acid Alleviates Peripheral ... Ganglioside monosialic acid potentially decreases severe utidelone plus capecitabine-induced peripheral neuropathy in metastatic breast cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01399

Prevention and Management of Chemotherapy-Induced ... Ganglioside-monosialic acid seemed to be effective in preventing taxane-induced peripheral neuropathy in Chinese patients, but this should ...