Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT05751668
Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel
A Phase 2 study testing Paclitaxel, Monosialotetrahexosylganglioside and Questionnaire Administration in people with Anatomic Stage IV Breast Cancer AJCC v8 and Chemotherapy-Induced Peripheral Neuropathy, run by Alliance for Clinical Trials in Oncology at 33 sites in United States.
Trial summary
This early phase/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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Chemotherapy-Induced Peripheral Neuropathy, Metastatic Breast Carcinoma
- What is being tested?
- Paclitaxel, Monosialotetrahexosylganglioside and Questionnaire Administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 33 sitesUnited States
- Study dates
- 2 Nov 2023to 15 Nov 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 100,000/mm^3
- Creatinine =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- No planned use of duloxetine
- No planned use of cryotherapy, compression therapy, or cryocompression therapy at study entry
Who cannot join
- N/A
Trial locations and contacts
33 sites in 1 country.
33 sites in 1 country
United States33 sites
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Saint Luke's Hospital
Chesterfield, Missouri, 63017
Morton Plant Hospital
Clearwater, Florida, 33756
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Mount Sinai Medical Center
Miami Beach, Florida, 33140
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303
Saint Anthony's Hospital Cancer Care Center
St. Petersburg, Florida, 33705
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, 43623
Legacy Meridian Park Hospital
Tualatin, Oregon, 97062
Legacy Cancer Institute Medical Oncology and Day Treatment
Vancouver, Washington, 98684
Legacy Salmon Creek Hospital
Vancouver, Washington, 98686
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476
About this study
Official title: An Early Phase and Phase II Clinical Trial to Evaluate Ganglioside-Monosialic Acid (GM1) for Preventing Paclitaxel-Associated Neuropathy
This early phase/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 tumor 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To obtain data to further support the safety of increasing monosialotetrahexosylganglioside (GM1) doses when given on day 1, concomitantly with paclitaxel. (Early phase) II. To evaluate the preliminary efficacy of GM1 compared with placebo at preventing paclitaxel-induced peripheral neuropathy sensory symptoms as measured by the six 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. (Phase II)
SECONDARY OBJECTIVES:
- To obtain additional data to support the safety of GM1 in the treated population. (Phase II) II. To obtain data to support that GM1 looks promising for preventing/decreasing acute paclitaxel pain syndrome as measured by the Acute Pain Syndrome Questionnaire. (Phase II)
EXPLORATORY OBJECTIVES:
- Conduct of this clinical trial provides the opportunity to facilitate the better understanding of the natural history of paclitaxel-induced neuropathy, akin to what is being examined in a currently active trial, S1714. (Phase II) II. This clinical trial also provides an opportunity to conduct correlative studies to understand the mechanism of CIPN and/or identify biomarkers of CIPN or GM1 efficacy. (Phase II) III. To obtain efficacy data to assess the impact of GM1 on the anti-tumor activity of paclitaxel as evaluated by progression-free survival and overall survival. (Phase II)
OUTLINE: This is an early phase dose-escalation study of GM1 followed by a phase II study.
EARLY PHASE: Patients receive GM1 intravenously (IV) 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.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: 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.
ARM II: 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.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Chemotherapy-Induced Peripheral Neuropathy, Metastatic Breast Carcinoma
- Being tested
- Paclitaxel, Monosialotetrahexosylganglioside, Questionnaire Administration, Quality-of-life assessment, Placebo Administration
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol
Given IV
MonosialotetrahexosylgangliosideDrug
Also called Ganglioside GM-1, GM-1, GM1, Monosialoanglioside GM1
Given IV
Questionnaire AdministrationOther
Ancillary Studies
Quality-of-life assessmentOther
Ancillary Studies
Placebo AdministrationDrug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Paclitaxel; Other: Questionnaire Administration; Other: Quality-of-life assessment; Drug: Placebo Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Up to one year
Secondary outcomes (6)
Percentage of patients who received full planned dose of paclitaxel
Binary endpoint (yes or no). will graphically look at the percentages of patients receiving full planned paclitaxel doses per cycle within each arm. This is an indirect measure of paclitaxel-induced peripheral neuropathy, as most patients who stop receiving full dose paclitaxel do so because of paclitaxel-induced peripheral neuropathy troubles. In addition to graphically displaying the percentage of patients who receive full dose paclitaxel at each cycle, and according to arm, will make a between-arm comparison in terms of changes in the probability of receiving full dose paclitaxel over the 12 cycles of treatment. For latter analysis, the generalized estimating equations approach will be applied, with inference based on the empirical or sandwich variance estimator.
Measured: up to 1 year
• Sensory subscale of the European Organization of Research and Treatment of Cancer (EORTC) QLQ-CIPN20
Serially measured. Item scores are totaled and linearly converted to a 0-100 point scale with higher scores representing fewer symptoms or better quality of life. Will use the area under the curve (AUC) to summarize the serially measured sensory subscale scores. Patients will be analyzed in the arms to which they were randomized. In order to adjust for the stratification factors, the AUC will be computed for the two arms based on estimated parameters from a repeated-measures (means) mixed model.
Measured: Up to 1 year
Rate of grade 3+ Adverse Events
The proportion of patients experiencing a grade 3+ adverse events or toxicities will be described for each treatment arm, and will also be compared between the arms using Fisher's exact tests. Additional summaries and test will be performed as needed.
Measured: Up to 1 year
• Serially measured patient-reported outcome that best describes the patients' aches/pains at its worst in the last 24 hours
Within each arm, the mean score at each time point will be plotted longitudinally for the endpoints measuring aches and pains at its worst. The functional form of the relationship between time and each of these three patient-reported acute neuropathy items is not known. Penalized splines, a smoothing technique which does not require strong assumptions concerning the functional form of the pattern of change in the mean response, will be applied to these longitudinal data. In the two-arm setting (GM1 vs placebo) time trends will be incorporated in a non-parametric fashion, thereby allowing the mean response to change in a highly non-linear, but not predetermined, way. The intervention effect will be incorporated in the model in a parametric fashion, thereby allowing a relatively simple, but powerful, test of the intervention effect on changes in the mean response over time.
Measured: 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
Within each arm, the mean score at each time point will be plotted longitudinally for the endpoints measuring aches and pains at its least. The functional form of the relationship between time and each of these three patient-reported acute neuropathy items is not known. Penalized splines, a smoothing technique which does not require strong assumptions concerning the functional form of the pattern of change in the mean response, will be applied to these longitudinal data. In the two-arm setting (GM1 vs placebo) time trends will be incorporated in a non-parametric fashion, thereby allowing the mean response to change in a highly non-linear, but not predetermined, way. The intervention effect will be incorporated in the model in a parametric fashion, thereby allowing a relatively simple, but powerful, test of the intervention effect on changes in the mean response over time.
Measured: in the preceding 24 hours
• Serially measured patient-reported outcome that best describes the patients' aches/pains on the average in the last 24 hours
Within each arm, the mean score at each time point will be plotted longitudinally for the endpoints measuring aches and pains on average. The functional form of the relationship between time and each of these three patient-reported acute neuropathy items is not known. Penalized splines, a smoothing technique which does not require strong assumptions concerning the functional form of the pattern of change in the mean response, will be applied to these longitudinal data. In the two-arm setting (GM1 vs placebo) time trends will be incorporated in a non-parametric fashion, thereby allowing the mean response to change in a highly non-linear, but not predetermined, way. The intervention effect will be incorporated in the model in a parametric fashion, thereby allowing a relatively simple, but powerful, test of the intervention effect on changes in the mean response over time.
Measured: in the preceding 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start2 Nov 2023
- Primary completion15 Nov 2026 (estimated)
- Study completion15 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05751668
- Sponsor's protocol ID
- A222101
- Other IDs
- NCI-2022-04929
- Status last verified
- Oct 2026
- First submitted
- 21 Feb 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No