Back to resultsA Study of Monosialic Gangliosides to Prevent Albumin-bound Paclitaxel Neurotoxicity
Primary Purpose
Early Breast Cancer
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
monosialic gangliosides
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Early Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Female patients diagnosed with early breast cancer by histology;
- Age ≥18 years old and ≤75 years old
- It is expected that the standard chemotherapy regimen containing albumin paclitaxel will be used in the adjuvant / neo-adjuvant chemotherapy regimen. The standard scheme includes: a. Albumin paclitaxel adopts a single-week regimen, 125-150mg / m2 for 12 weeks; b. Albumin paclitaxel Take a 3-week regimen, 260 mg / m2, for a total of 4 cycles. The plan must not contain platinum and other types of purple shirt drugs;
- ECOG score of the patient is ≤1;
- Expected survival time ≥ 3 months;
- The function level of main organs must meet the following requirements (no blood transfusion and no use of leukocyte or platelet rising drugs within 2 weeks before screening) Blood routine: neutrophil (ANC) ≥ 1.5x 109 / L; platelet (PLT) ≥ 90x109 / L; hemoglobin (Hb) ≥ 90g / L Blood biochemical total bilirubin (TBIL) ≤ 1.5xULN; alanine aminotransferase (AST) and aspartate aminotransferase (AST) not exceeding 2 × ULN; blood urea nitrogen (BUN) and creatinine (CR) below 1.5 × ULN;
- FACT-Ntx score is 44 points in the screening period
- Sign the informed consent.
Exclusion Criteria:
- There are any toxic events of the peripheral nervous system before enrollment, including: FACT-Ntx subscale score <44; ≥ 1 level of peripheral toxicity according to the CTCAE version 4.0 scale; all other pathological symptoms or diseases may affect Assessment of adverse neurotoxic effects;
- Patients receiving other medications may cause similar adverse neurotoxic effects within 4 weeks before treatment with this regimen, or they may also receive neurotoxic medications at the same time. Including paclitaxel or analogues; vinca alkaloids or analogues; platinums or analogues; cytarabine, thalidomide, bortezomib or cabazine; other drugs or treatments may cause peripheral neurotoxicity;
- Patients with poor overall condition and ECOG score> 1;
- pregnant or lactating women;
- Patients who also suffer from other neurological abnormalities cannot accurately record the occurrence and severity of neurotoxicity;
- The patient is known to be allergic to the test drug or excipient ingredients of these products;
- Patients with hereditary abnormalities of glucose and lipid metabolism (gangliopathies, such as idiopathic and retinopathy of triad families);
- Patients not suitable for ganglioside treatment;
- Patients with severe concurrent diseases may endanger safety and interfere with scheduled treatment, or the combination of diseases may affect the completion of the study, depending on the judgment of the investigator.
- Patients with a clear history of neurological or mental disorders, including epilepsy or dementia.
Sites / Locations
- Henan Cancer Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
monosialic ganglioside
Placebo
Arm Description
On the days -1, 1, and 2 of albumin paclitaxel application, 80 mg of monosialic ganglioside were applied (monosialic ganglioside was a single infusion)
The control group received placebo on days -1, 1, and 2 of albumin paclitaxel (placebo as a single infusion)
Outcomes
Primary Outcome Measures
Functional Assessment of Cancer Treatment Neurotoxicity Scale （FACT-Ntx）score
FACT-Ntx scale score 2 weeks after 4 cycles of albumin-bound paclitaxel chemotherapy. (The FACT-Ntx subscale includes 11 items, each of which is divided into 5 scoring levels: 0, 1, 2, 3, 4, and a total score of 44. Higher scores indicate lower side effects). The scale is graded 0-4. A low score indicates a good effect.
Secondary Outcome Measures
CTCAE Version 4.0 score
neurotoxicity evaluated by NCI-CTCAE version 4.0 grading scale which classified symptoms as grade 0, 1, 2, 3, or 4. Higher scores indicate more severe neurotoxicity.
The NCI-CTCAE version 4.0 assessments were performed at 2 weeks after each course of chemotherapy. Additional long-term assessments were performed at 3 months, 6 months and 1 year after the end of chemotherapy.
Functional Assessment of Cancer Treatment Neurotoxicity Scale （FACT-Ntx）score
The scale is graded 0-4. A low score indicates a good effect.
functional assesment of cancer therapy-taxane （FACT-Taxane）score
Compare FACT-Taxane outcome in treatment vs placebo groups at 2 weeks after 4 cycles of chemotherapy. Lower scores indicate worse functional status. Total possible range is 0 to 64.The paclitaxel therapeutic function assessment scale is mainly used to assess baseline peripheral neurotoxicity, and a lower score indicates less neurotoxicity.
Functional Assessment of Cancer Therapy-General （FACT-G）score
Compare FACT-G outcome in treatment vs placebo groups at 2 weeks after 4 cycles of chemotherapy. Lower scores indicate worse functional status. Total possible range is 0 to 128.The low score of the cancer patients' quality of life scale indicates that the patients' quality of life is better.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04222790
Brief Title
A Study of Monosialic Gangliosides to Prevent Albumin-bound Paclitaxel Neurotoxicity
Official Title
A Multicenter, Double-blind, Randomized Controlled Phase II Clinical Study of Monosialic Gangliosides to Prevent Albumin-bound Paclitaxel Neurotoxicity
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
August 28, 2020 (Actual)
Primary Completion Date
April 21, 2022 (Actual)
Study Completion Date
April 21, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Henan Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Taxane-induced peripheral neuropathy (TIPN) caused by paclitaxel is a dose-limiting toxicity. The main symptoms of discomfort are numbness, tingling, and burning sensations in the glove-sock-like distribution of the limbs. At present, there are few effective methods for clinical treatment of TIPN, and there is no widely agreed consensus on effective treatment in the world. Therefore, it is of great clinical significance and practical value to carry out clinical research to explore drugs to relieve TIPN.
Detailed Description
Taxane induced peripheral neuropathy (TIPN) caused by taxol is a dose limiting toxicity. The discomfort symptoms mainly include numbness, tingling and burning sensation in the glove sock like distribution of the extremities. This symptom can lead to limited activity, damage the self-care ability and social function of patients, and significantly reduce the quality of life of patients, At the same time, it may lead to early termination of chemotherapy and affect tumor treatment. The overall incidence of TIPN is very high. Many studies show that the incidence of TIPN is as high as 80%. CTCAE classifies it into 5 grades, and 25% - 30% of patients can have serious neurotoxicity. However, there are few effective methods for clinical treatment of TIPN, and there is no international consensus on effective treatment. Therefore, it is of great clinical significance and practical value to carry out clinical research on drugs to alleviate TIPN.
Monosialoganglioside (GM1), a member of the ganglioside family, is a kind of glycosylsphingolipid containing sialic acid on the cell membrane of mammalian animals. It is an endogenous substance. Gangliosides are mainly distributed in the outer layer of the cell membrane, especially on nerve endings and dendrites. It is most abundant and mainly expressed in the cell membrane of neurons. It participates in a variety of neurobiological activities, including neuronal differentiation Plasticity and cell survival. There is evidence that the application of GM1 can protect nerve cells, promote the recovery of neural function, and reduce the time of disability. Recent clinical studies on gangliosides have also shown promising results. GM1 effectively alleviates the neurotoxicity caused by docetaxel.
Although there have been previous studies on the effect of gangliosides on relieving the neurotoxicity of docetaxel, studies on the effect of gangliosides on relieving albumin bound paclitaxel have not been seen, and prospective clinical research data of large samples are lacking. In conclusion, the researchers hope to explore effective and reliable drugs to alleviate the peripheral neurotoxicity of albumin bound paclitaxel.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
159 (Actual)
8. Arms, Groups, and Interventions
Arm Title
monosialic ganglioside
Arm Type
Experimental
Arm Description
On the days -1, 1, and 2 of albumin paclitaxel application, 80 mg of monosialic ganglioside were applied (monosialic ganglioside was a single infusion)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The control group received placebo on days -1, 1, and 2 of albumin paclitaxel (placebo as a single infusion)
Intervention Type
Drug
Intervention Name(s)
monosialic gangliosides
Other Intervention Name(s)
experience group
Intervention Description
The experimental group received 80 mg of monosialic gangliosides (GM1) on days -1, 1, and 2 of albumin paclitaxel (GM1 is a single infusion).
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
control group
Intervention Description
The control group received placebo on days -1, 1, and 2 of albumin paclitaxel (placebo as a single infusion)
Primary Outcome Measure Information:
Title
Functional Assessment of Cancer Treatment Neurotoxicity Scale （FACT-Ntx）score
Description
FACT-Ntx scale score 2 weeks after 4 cycles of albumin-bound paclitaxel chemotherapy. (The FACT-Ntx subscale includes 11 items, each of which is divided into 5 scoring levels: 0, 1, 2, 3, 4, and a total score of 44. Higher scores indicate lower side effects). The scale is graded 0-4. A low score indicates a good effect.
Time Frame
2 weeks after 4 cycles of albumin-bound paclitaxel chemotherapy
Secondary Outcome Measure Information:
Title
CTCAE Version 4.0 score
Description
neurotoxicity evaluated by NCI-CTCAE version 4.0 grading scale which classified symptoms as grade 0, 1, 2, 3, or 4. Higher scores indicate more severe neurotoxicity.
The NCI-CTCAE version 4.0 assessments were performed at 2 weeks after each course of chemotherapy. Additional long-term assessments were performed at 3 months, 6 months and 1 year after the end of chemotherapy.
Time Frame
1 month Day 1 of Week 1 to 1 year after the last course of chemotherapy
Title
Functional Assessment of Cancer Treatment Neurotoxicity Scale （FACT-Ntx）score
Description
The scale is graded 0-4. A low score indicates a good effect.
Time Frame
3 months, 6 months, and 12 months after 4 cycles of chemotherapy
Title
functional assesment of cancer therapy-taxane （FACT-Taxane）score
Description
Compare FACT-Taxane outcome in treatment vs placebo groups at 2 weeks after 4 cycles of chemotherapy. Lower scores indicate worse functional status. Total possible range is 0 to 64.The paclitaxel therapeutic function assessment scale is mainly used to assess baseline peripheral neurotoxicity, and a lower score indicates less neurotoxicity.
Time Frame
2 weeks after 4 cycles of albumin-bound paclitaxel chemotherapy
Title
Functional Assessment of Cancer Therapy-General （FACT-G）score
Description
Compare FACT-G outcome in treatment vs placebo groups at 2 weeks after 4 cycles of chemotherapy. Lower scores indicate worse functional status. Total possible range is 0 to 128.The low score of the cancer patients' quality of life scale indicates that the patients' quality of life is better.
Time Frame
2 weeks after 4 cycles of albumin-bound paclitaxel chemotherapy
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patients diagnosed with early breast cancer by histology;
Age ≥18 years old and ≤75 years old
It is expected that the standard chemotherapy regimen containing albumin paclitaxel will be used in the adjuvant / neo-adjuvant chemotherapy regimen. The standard scheme includes: a. Albumin paclitaxel adopts a single-week regimen, 125-150mg / m2 for 12 weeks; b. Albumin paclitaxel Take a 3-week regimen, 260 mg / m2, for a total of 4 cycles. The plan must not contain platinum and other types of purple shirt drugs;
ECOG score of the patient is ≤1;
Expected survival time ≥ 3 months;
The function level of main organs must meet the following requirements (no blood transfusion and no use of leukocyte or platelet rising drugs within 2 weeks before screening) Blood routine: neutrophil (ANC) ≥ 1.5x 109 / L; platelet (PLT) ≥ 90x109 / L; hemoglobin (Hb) ≥ 90g / L Blood biochemical total bilirubin (TBIL) ≤ 1.5xULN; alanine aminotransferase (AST) and aspartate aminotransferase (AST) not exceeding 2 × ULN; blood urea nitrogen (BUN) and creatinine (CR) below 1.5 × ULN;
FACT-Ntx score is 44 points in the screening period
Sign the informed consent.
Exclusion Criteria:
There are any toxic events of the peripheral nervous system before enrollment, including: FACT-Ntx subscale score <44; ≥ 1 level of peripheral toxicity according to the CTCAE version 4.0 scale; all other pathological symptoms or diseases may affect Assessment of adverse neurotoxic effects;
Patients receiving other medications may cause similar adverse neurotoxic effects within 4 weeks before treatment with this regimen, or they may also receive neurotoxic medications at the same time. Including paclitaxel or analogues; vinca alkaloids or analogues; platinums or analogues; cytarabine, thalidomide, bortezomib or cabazine; other drugs or treatments may cause peripheral neurotoxicity;
Patients with poor overall condition and ECOG score> 1;
pregnant or lactating women;
Patients who also suffer from other neurological abnormalities cannot accurately record the occurrence and severity of neurotoxicity;
The patient is known to be allergic to the test drug or excipient ingredients of these products;
Patients with hereditary abnormalities of glucose and lipid metabolism (gangliopathies, such as idiopathic and retinopathy of triad families);
Patients not suitable for ganglioside treatment;
Patients with severe concurrent diseases may endanger safety and interfere with scheduled treatment, or the combination of diseases may affect the completion of the study, depending on the judgment of the investigator.
Patients with a clear history of neurological or mental disorders, including epilepsy or dementia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenzhen Liu
Organizational Affiliation
Henan Cancer Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
12. IPD Sharing Statement
Learn more about this trial
A Study of Monosialic Gangliosides to Prevent Albumin-bound Paclitaxel Neurotoxicity
We'll reach out to this number within 24 hrs