Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II)

NCT05751668 | Suspended Phase 2 DMC

• 2 other identifiers: A222101NCI-2022-04929
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 33

Brief Summary

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Chemotherapy-Induced Peripheral Neuropathy; Metastatic Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (Early phase)

  Defined as the highest dose level that induces dose-limiting toxicity in less than one-third of patients (less than 1 out of 3 or less than 2 out of a maximum of 6 new patients).The constellation of adverse events as scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version (v) 5.0 (CTCAE v5.0) will be summarized by reporting the number and percentage of patients. Specifically, the number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion. Further, all adverse events will be listed by system organ class and preferred term.

  6-7 months

• Composite response (Phase II)

  Reflects sensory paclitaxel-induced peripheral neuropathy symptom severity and onset. Measured using 6 individual Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness (N), tingling (T) and pain in the fingers/hands and toes/feet. Will calculate the highest (worst) N, T, and pain sensory score obtained anytime during paclitaxel exposure. Response is defined as a patient reporting a highest score of =\< 2 without discontinuing the study due to sensory paclitaxel-induced peripheral neuropathy. Chi-squared test will be used. Will report the proportion of patients achieving a composite response in each arm as well as the difference in proportions along with the 90% confidence interval. Will report the estimated odds ratio (monosialotetrahexosylganglioside \[GM1\]/placebo) and the corresponding 90% confidence interval for the true, but unknown odds ratio. Multiple logistic regression will be used to estimate the intervention

  Up to one year

Secondary Outcomes (6)

• Percentage of patients who received full planned dose of paclitaxel

  up to 1 year

• • Sensory subscale of the European Organization of Research and Treatment of Cancer (EORTC) QLQ-CIPN20

  Up to 1 year

• Rate of grade 3+ Adverse Events

  Up to 1 year

• • Serially measured patient-reported outcome that best describes the patients' aches/pains at its worst in the last 24 hours

  In the preceding 24 hours

• Serially measured patient-reported outcome that best describes the patients' aches/pains at its least in the last 24 hours

  in the preceding 24 hours

Other Outcomes (6)

• Progression free survival (PFS)

  Up to 4 years after the end of GM1 treatment

• Overall survival (OS)

  Up to 4 years after the end of GM1 treatment

• Serially measured total score of the EORTC QLQ-CIPN20

  On day 1 of each dose prior to GM1, monthly after the end of GM1, at 8, 12, 16, 20, and 24 months after last study treatment

Study Arms (2)

Arm I (paclitaxel, GM1)

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Monosialotetrahexosylganglioside; Other: Questionnaire Administration; Other: Quality-of-life assessment

Arm II (paclitaxel, placebo)

PLACEBO COMPARATOR

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.

Drug: Paclitaxel; Other: Questionnaire Administration; Other: Quality-of-life assessment; Drug: Placebo Administration

Interventions

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol

Arm I (paclitaxel, GM1); Arm II (paclitaxel, placebo)

Monosialotetrahexosylganglioside DRUG

Given IV

Also known as: Ganglioside GM-1, GM-1, GM1, Monosialoanglioside GM1

Arm I (paclitaxel, GM1)

Questionnaire Administration OTHER

Ancillary Studies

Arm I (paclitaxel, GM1); Arm II (paclitaxel, placebo)

Quality-of-life assessment OTHER

Ancillary Studies

Arm I (paclitaxel, GM1); Arm II (paclitaxel, placebo)

Placebo Administration DRUG

Given IV

Arm II (paclitaxel, placebo)

Eligibility Criteria

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

You may qualify if:

• Documentation of disease: Histologic diagnosis of metastatic breast cancer in women or men
• Prior treatment- No previous exposure to GM1
• Planned administration of paclitaxel, either given weekly, or weekly 3 weeks on/1 week off, to patients with metastatic cancer at a dose of 80 mg/m\^2
• No planned treatment with concurrent immunotherapy
• Score of 1 (none) and/or 2 (a little) on the six individual European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)- chemotherapy-induced peripheral neuropathy (CIPN)20 questions that quantify numbness (N), tingling (T), and pain in the fingers/hands and toes/feet (Items #31-36)
• No diagnosis of fibromyalgia
• No history of significant respiratory tract infection and/or infectious diarrhea within 14 days before registration
• No history of stroke or cerebrovascular accident in the past 6 months prior to registration
• No history of diagnosed neurologic or psychiatric disorders, including epilepsy or dementia
• For women of childbearing potential, not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Therefore, for women of childbearing potential, a negative pregnancy test done =\< 7 days prior to registration is required. Of note, a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Ability to complete questionnaires by themselves or with assistance
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English and/or Spanish
• Persons with impaired decision making such that they cannot understand the benefits or risks of trial participation, per the judgement of the consenting clinician, will not be eligible
• Age \>= 18 years

You may not qualify if:

• N/A

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (33)

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Saint Anthony's Hospital Cancer Care Center

St. Petersburg, Florida, 33705, United States

Location

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023, United States

Location

Mercy Hospital

Cedar Rapids, Iowa, 52403, United States

Location

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, 50325, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309, United States

Location

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, 50314, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Saint Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Southeastern Medical Oncology Center-Clinton

Clinton, North Carolina, 28328, United States

Location

Southeastern Medical Oncology Center-Goldsboro

Goldsboro, North Carolina, 27534, United States

Location

Southeastern Medical Oncology Center-Jacksonville

Jacksonville, North Carolina, 28546, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, 43623, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Mount Hood Medical Center

Gresham, Oregon, 97030, United States

Location

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

Location

Legacy Meridian Park Hospital

Tualatin, Oregon, 97062, United States

Location

Legacy Cancer Institute Medical Oncology and Day Treatment

Vancouver, Washington, 98684, United States

Location

Legacy Salmon Creek Hospital

Vancouver, Washington, 98686, United States

Location

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, 54548, United States

Location

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, 54868, United States

Location

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, 54482, United States

Location

Marshfield Medical Center - Weston

Weston, Wisconsin, 54476, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Taxes; G(M1) Ganglioside

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Gangliosides; Acidic Glycosphingolipids; Glycosphingolipids; Glycolipids; Glycoconjugates; Carbohydrates; Lipids; Sphingolipids; Membrane Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 2, 2023
• Study Start: November 2, 2023
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 15, 2032
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (33)