GM1 for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer

Recruiting at 37 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

Trial Summary

What is the purpose of this trial?

This phase II trial tests the safety, side effects, and best dose of monosialotetrahexosylganglioside (GM1) and whether it works in reducing or preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) who are receiving treatment with paclitaxel. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Exposure to chemotherapy drugs like paclitaxel may cause a side effect called CIPN, which is a condition of weakness, numbness, and pain from nerve damage (usually in the hands and feet). GM1 is a part of the body's natural system that insulates nerves and helps to protect nerves from damage. Giving GM1 may help reduce or prevent CIPN in breast cancer patients receiving treatment with paclitaxel.

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.

What data supports the effectiveness of the drug GM1 for preventing chemotherapy-induced peripheral neuropathy in breast cancer patients?

A meta-analysis found that Ganglioside-monosialic acid (GM1) may be effective in preventing chemotherapy-induced peripheral neuropathy, a common side effect of cancer treatment that affects nerves and can cause pain and numbness. ^{1 2 3 4 5}

Is GM1 safe for humans?

GM1 has been studied in humans for its ability to protect nerves, particularly in patients undergoing chemotherapy. In these studies, GM1 was shown to reduce nerve damage without affecting the effectiveness of the chemotherapy, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does the drug GM1 differ from other treatments for chemotherapy-induced peripheral neuropathy in breast cancer?

GM1 is unique because it is a neuroprotective agent that helps repair nerves, which is different from other treatments that may not directly target nerve protection. It has been shown to reduce the severity of neuropathy in patients undergoing chemotherapy, without affecting the effectiveness of the cancer treatment. ^{6 7 8 9 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis. [2022]

2. Netherlands 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. [2022]

5. United States 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. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial. [2020]

7. France pubmed.ncbi.nlm.nih.gov

The effect of monosialotetrahexosylganglioside (GM1) in prevention of oxaliplatin induced neurotoxicity: a retrospective study. [2020]

8. United States 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of GM1 ganglioside following parenteral administration. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

GM1 ganglioside counteracts cholinergic and behavioral deficits induced in the rat by intracerebral injection of vincristine. [2019]