Clinical trial NCT05751668: Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II)
Official title: An Early Phase and Phase II Clinical Trial to Evaluate Ganglioside-Monosialic Acid (GM1) for Preventing Paclitaxel-Associated Neuropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Anatomic Stage IV Breast Cancer AJCC v8
Chemotherapy-Induced Peripheral Neuropathy
Metastatic Breast Carcinoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-03-02
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* N/A

Primary outcomes:
measure: Maximum Tolerated Dose (Early phase)
timeFrame: 6-7 months
measure: Composite response (Phase II)
timeFrame: Up to one year
Secondary outcomes:
measure: Percentage of patients who received full planned dose of paclitaxel
timeFrame: up to 1 year
measure: • Sensory subscale of the European Organization of Research and Treatment of Cancer (EORTC) QLQ-CIPN20
timeFrame: Up to 1 year
measure: Rate of grade 3+ Adverse Events
timeFrame: Up to 1 year
measure: • Serially measured patient-reported outcome that best describes the patients' aches/pains at its worst in the last 24 hours
timeFrame: In the preceding 24 hours
measure: Serially measured patient-reported outcome that best describes the patients' aches/pains at its least in the last 24 hours
timeFrame: in the preceding 24 hours
measure: • Serially measured patient-reported outcome that best describes the patients' aches/pains on the average in the last 24 hours
timeFrame: in the preceding 24 hours
Other outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 4 years after the end of GM1 treatment
measure: Overall survival (OS)
timeFrame: Up to 4 years after the end of GM1 treatment
measure: Serially measured total score of the EORTC QLQ-CIPN20
timeFrame: 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
measure: Patient-reported severity and interference of numbness or tingling in hands or feet
timeFrame: 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
measure: Serially measured patient-reported aggregate scores
timeFrame: 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
measure: Serially measured patient-reported total score
timeFrame: 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
Locations:
city: Irvine
country: United States
facility: UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Saint Petersburg
country: United States
facility: Saint Anthony's Hospital Cancer Care Center
state: Florida
city: Ankeny
country: United States
facility: UI Health Care Mission Cancer and Blood - Ankeny Clinic
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Clive
country: United States
facility: UI Health Care Mission Cancer and Blood - West Des Moines Clinic
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: UI Health Care Mission Cancer and Blood - Des Moines Clinic
state: Iowa
city: Des Moines
country: United States
facility: UI Health Care Mission Cancer and Blood - Laurel Clinic
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center at Saint Cloud Hospital
state: Minnesota
city: Chesterfield
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Clinton
country: United States
facility: Southeastern Medical Oncology Center-Clinton
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center-Goldsboro
state: North Carolina
city: Jacksonville
country: United States
facility: Southeastern Medical Oncology Center-Jacksonville
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers-Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Vancouver
country: United States
facility: Legacy Cancer Institute Medical Oncology and Day Treatment
state: Washington
city: Vancouver
country: United States
facility: Legacy Salmon Creek Hospital
state: Washington
city: Eau Claire
country: United States
facility: Marshfield Medical Center-EC Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center-Marshfield
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Medical Center - Minocqua
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Medical Center-Rice Lake
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Medical Center-River Region at Stevens Point
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Medical Center - Weston
state: Wisconsin
Study officials:
References: