Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nervous System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Peripheral Nervous System Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

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Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Bortezomib

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

each patient in this arm received velcade+dexamethasone (VD) regimen（bortezomib,1.3mg/㎡，subcutaneously injection，d1,8,15,22；dexamethasone,20mg d1-2, 8-9,15-16,22-23）every 4 weeks; and monosialotetrahexosylganglioside was used at the dosage of 100mg/d intravenously at d1-2,8-9,15-16,22-23 every cycle.

Monosialotetrahexosylganglioside

Zhong-jun Xia, M.D.

Liang Wang, M.D.

Bortezomib was an important drug in the treatment of multiple myeloma (MM),and peripheral neuropathy (PN) is a significant dose-limiting toxicity of bortezomib that typically occurs within the first courses of bortezomib, reaches a plateau at cycle 5. Up to now, no effective prophylaxis have been developed for PN. Monosialotetrahexosylganglioside, a nerve-protecting drug,was often used to promote growth of nerve, and function restoration of damaged nerve.Thus,the investigators hypothesized that combination of Monosialotetrahexosylganglioside and bortezomib can reduce the incidence rate of peripheral neuropathy (PN) and promote the relief of peripheral neuropathy (PN) in multiple myeloma (MM) patients.

Efficacy of Monosialotetrahexosylganglioside in the Prophylactic Treatment of Bortezomib-induced Peripheral Neuropathy

Phase 2 Study of Concurrent Monosialotetrahexosylganglioside in the Prophylactic Treatment of Bortezomib-induced Peripheral Neuropathy in Patients of Multiple Myeloma

the grade of peripheral neuropathy (PN) was recorded according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

the duration of peripheral neuropathy means the time from the onset time of peripheral neuropathy (PN) to the relief time of PN

The criteria for CR was according to International Myeloma Working Group Uniform Response Criteria

Sun Yat-sen University

Professor

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Carcinoma

Asthenia

Hypesthesia

Breast Diseases

Skin Diseases

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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.

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.

Questionnaire Administration

Quality-of-life assessment

Placebo Administration

Elizabeth Cathcart-Rake, MD

Aishwarya Vijendran

Site Public Contact

Ritesh Parajuli

Vijaya K. Gadiyaram

Deborah W. Wilbur

Joshua Lukenbill

Elizabeth Cathcart-Rake

Donald J. Jurgens

Joseph Sokhn

Samer S. Kasbari

Rex B. Mowat

Wajeeha Razaq

Mei Dong

Patcharin Tanawattanacharoen

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.

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

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

An Early Phase and Phase II Clinical Trial to Evaluate Ganglioside-Monosialic Acid (GM1) for Preventing Paclitaxel-Associated Neuropathy

Distributions of PFS times will be estimated using Kaplan-Meier methodology.

Distributions of OS times will be estimated using Kaplan-Meier methodology.

Will use the AUC to summarize the serially measured EORTC QLQ-CIPN20 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.

As measured by the Patient Reported Outcomes version CTCAE (PRO-CTCAE). The maximum grade for each of these events will be recorded for each patient and frequency tables will be generated and presented according to treatment arm. The descriptive analysis of the PRO-CTCAE endpoints will be based on the safety population and analyzed according to the treatment actually received.

Measured by the 11-item Functional Assessment of Cancer Therapy - Gynecologic Oncology Group-Neurotoxicity 4. Will tabulate all available serially measured PROs at each protocol defined time point and within each arm; furthermore, will graphically display the longitudinal PROs over time. Will compare and contrast the descriptive findings between these CIPN-measuring instruments in this trial and in the corresponding longitudinal data obtained in S1714. No inferential statistics will be generated. Further, these descriptive summaries will be used to better understand these instruments.

Measured by the 5-item Patient Reported Outcomes Measurement Information System-Neuropathic Pain Quality scale. Will tabulate all available serially measured PROs at each protocol defined time point and within each arm; furthermore, will graphically display the longitudinal PROs over time. Will compare and contrast the descriptive findings between these CIPN-measuring instruments in this trial and in the corresponding longitudinal data obtained in S1714. No inferential statistics will be generated. Further, these descriptive summaries will be used to better understand these instruments.

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.

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

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.

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy of Monosialotetrahexosylganglioside in the Prophylactic Treatment of Bortezomib-induced Peripheral Neuropathy	NCT02093910	Multiple Myelom...	Monosialotetrah...	18 Years - 80 Years	Sun Yat-sen University
Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II)	NCT05751668	Anatomic Stage ... Chemotherapy-In... Metastatic Brea...	Paclitaxel Monosialotetrah... Questionnaire A... Quality-of-life... Placebo Adminis...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for monosialotetrahexosylganglioside