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Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer

Primary Purpose

Breast Cancer, Neoadjuvant Therapy

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Utidelone
Carboplatin
Epirubicin
Trastuzumab
Pertuzumab
Sponsored by
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Female patients who will receive initial treatment, 18-70 years of age; Newly diagnosed high-risk early stage (T1c-2, N1; T2, N0) and locally advanced (T1c-2, N2-3; T3-4, N0-3) breast cancer (tumor stage II, III), in which HR+/HER2- T2, N0 patients need to be accompanied by high-risk factors (histological grade 3 or Ki67 ≥ 20%). Triple negative breast cancer(TNBC), HER2 positive (Immunohistochemical(IHC)3+; IHC 2+, FISH amplification) breast cancer, HR negative HER2 IHC 2+ and undetermined result of FISH, HR positive HER2 negative (IHC 0,1+; 2+, FISH amplification) breast cancer confirmed by pathological test. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1 The blood routine examination was basically normal (CTCAE ≤ 1) within one week before enrollment (based on the normal values of each research center laboratory). No Human Granulocyte Colony Stimulating Factor(rhGCSF) or blood transfusion/erythropoietin(EPO) or other drugs were used within 14 days prior to enrollment. White blood cell count (WBC) ≥ 4 x109 / L; Neutrophil count (ANC) > 1.5x109 / L; Platelet count (PLT) ≥ 100×109/L Hemoglobin(Hb) ≥ 100g/L. The blood biochemistry examination was basically normal (CTCAE ≤ 1) within one week before enrollment (based on the normal values of each research center laboratory) Serum total bilirubin ≤ Upper limit of normal value(ULN); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 1.5×ULN; Alkaline phosphatase ≤ 2.5×ULN; Serum creatinine ≤ 1.5×ULN. Color Doppler echocardiography left ventricular Ejection fraction (LVEF) ≥ 55% Female patients with fertility must agree to use effective contraceptive methods during the study period and within 6 months of the last study medication. The Pregnancy test (urine or serum) must be negative Be willing and able to provide written informed consent/assent for the trial. Exclusion Criteria: Primary stage IV breast cancer; Inflammatory breast cancer; Bilateral primary breast cancer (including invasive cancer and carcinoma in situ); Previous anti-cancer treatment or radiotherapy for any malignant tumor, excluding cured cervical Carcinoma in situ, skin Basal-cell carcinoma and squamous cell carcinoma. Receive any sex hormone treatment (such as contraceptives, ovarian hormone replacement therapy, etc.), except for Ovarian function suppression(OFS)fertility protection, or any hormone drugs (such as Raloxifene, tamoxifen, or other selective estrogen receptor modulators) to treat osteoporosis or prevent breast cancer; The patient has undergone major surgery unrelated to breast cancer within 4 weeks before treatment or has not yet fully recovered; Symptomatic peripheral neuropathy CTCAE 5.0 grade ≥ 2 Serious cardio cerebral Vascular disease, including but not limited to the followings: History of congestive heart failure or systolic dysfunction (LVEF<50%); Angina pectoris requiring anti angina drugs; High risk uncontrolled arrhythmias or severe conduction abnormalities, such as ventricular arrhythmias that require clinical intervention, II-III degree atrioventricular block, etc; Under resting state, the average corrected Q-T interval(QTcF) of three 12 lead electrocardiogram examinations is>470ms; Clinically significant heart valve disease with cardiac dysfunction; Hypertension that cannot be controlled; History of myocardial infarction Allergic to any component of any drug in this protocol. Those who are not suitable for using Corticosteroid. Individuals with active infections who currently require systematic anti infection treatment. History of immune deficiency disease, including positive of HIV/AIDS, or other acquired or congenital immune deficiency diseases, or having a history of organ transplantation. Who had participated in other drug intervention clinical trials within the 28 days of randomization, or who is participating in another clinical trial or is using other investigational treatments. Individuals in pregnancy (positive Pregnancy test) and lactation. Any other comorbidities that interfere with the implementation of the treatment plan, or the researcher evaluate that the subject has a history of other serious systemic diseases, or other reasons lead to the patients is unsuitable to participate in this trial.

Sites / Locations

  • Cancer Hospital, Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

cohort 1 Triple-negative breast cancer

cohort 2 HR positive, HER2 negative breast cancer

cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer

Arm Description

Hormone Receptor(HR) negative, Human Epidermal Growth Factor Receptor 2(HER2 )negative breast cancer Drug: Utidelone in combination with carboplatin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin ,Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.

HR positive, HER2 negative, Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ hybridization(FISH)non-amplification breast cancer Drug: Utidelone in combination with Epirubicin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Epirubicin 75mg/m2 was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.

Drug: Utidelone in combination with carboplatin, trastuzumab and pertuzumab Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total. Trastuzumab 8mg/kg iv in first cycle on day 1, then 8mg/kg in the rest cycles; pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles. One treatment cycle is 21 days, and there are 6 cycles in total.

Outcomes

Primary Outcome Measures

Total pathological complete response (etpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is, (yp)N0)
Percentage of patients with absence of invasive neoplastic cells in ipsilateral lymph nodes and breast

Secondary Outcome Measures

Breast Pathologic Complete Response ((bpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is)
Percentage of patients whose pathological evaluation of hematoxylin and eosin-stained breast samples do not show any residual invasive carcinoma
Event Free Survival(EFS) of 2 years
Time from the first dose of study intervention administration to any of the following events: progression of disease that precludes surgery, local or distant recurrence after surgery, second primary malignancy (breast or other invasive cancers), or death due to any cause.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Graded according to the Common Terminology Criteria for Adverse Event (CTCAE) grade and changes in CTCAE grade
Patient reported outcome (PRO)
National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life;The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.
Patient reported outcome (PRO)
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-chemotherapy-induced peripheral neuropathy(CIPN) twenty-item scale (QLQ-CIPN20) was used to assess the quality of life.

Full Information

First Posted
July 18, 2023
Last Updated
August 1, 2023
Sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Collaborators
Chinese Academy of Medical Sciences Cancer Hospital,Shanxi Center, Chinese Academy of Medical Sciences Cancer Hospital,Shenzhen Center, First Affiliated Hospital of China Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05983094
Brief Title
Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer
Official Title
Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
September 1, 2026 (Anticipated)
Study Completion Date
September 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Collaborators
Chinese Academy of Medical Sciences Cancer Hospital,Shanxi Center, Chinese Academy of Medical Sciences Cancer Hospital,Shenzhen Center, First Affiliated Hospital of China Medical University

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
The purpose of this clinical trial is to evaluate the efficacy and safety of Utidelone based regimen as neoadjuvant treatment With High-risk Early-stage or Locally Advanced Breast Cancer.
Detailed Description
This is a single arm, multi-center study,three-cohort, prospective phase II study which will enroll 181 high-risk early-stage or locally advanced breast cancer patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Neoadjuvant Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Study of Utidelone based neoadjuvant treatment on early high-risk or locally advanced breast cancer
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
181 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cohort 1 Triple-negative breast cancer
Arm Type
Experimental
Arm Description
Hormone Receptor(HR) negative, Human Epidermal Growth Factor Receptor 2(HER2 )negative breast cancer Drug: Utidelone in combination with carboplatin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin ,Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.
Arm Title
cohort 2 HR positive, HER2 negative breast cancer
Arm Type
Experimental
Arm Description
HR positive, HER2 negative, Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ hybridization(FISH)non-amplification breast cancer Drug: Utidelone in combination with Epirubicin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Epirubicin 75mg/m2 was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.
Arm Title
cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
Arm Type
Experimental
Arm Description
Drug: Utidelone in combination with carboplatin, trastuzumab and pertuzumab Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total. Trastuzumab 8mg/kg iv in first cycle on day 1, then 8mg/kg in the rest cycles; pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles. One treatment cycle is 21 days, and there are 6 cycles in total.
Intervention Type
Drug
Intervention Name(s)
Utidelone
Intervention Description
Utidelone injection 30mg/m2, on days 1-5 of each cycle
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin Area under curve(AUC)6, iv, was administered on day 1
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Description
Epirubicin 75mg/m2 was administered on day 1
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab 8mg/kg iv in first cycle on day 1, then 6mg/kg in the rest cycles
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Intervention Description
Pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles
Primary Outcome Measure Information:
Title
Total pathological complete response (etpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is, (yp)N0)
Description
Percentage of patients with absence of invasive neoplastic cells in ipsilateral lymph nodes and breast
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Breast Pathologic Complete Response ((bpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is)
Description
Percentage of patients whose pathological evaluation of hematoxylin and eosin-stained breast samples do not show any residual invasive carcinoma
Time Frame
24 months
Title
Event Free Survival(EFS) of 2 years
Description
Time from the first dose of study intervention administration to any of the following events: progression of disease that precludes surgery, local or distant recurrence after surgery, second primary malignancy (breast or other invasive cancers), or death due to any cause.
Time Frame
24 months
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Graded according to the Common Terminology Criteria for Adverse Event (CTCAE) grade and changes in CTCAE grade
Time Frame
Through study completion,an average of 1 year
Title
Patient reported outcome (PRO)
Description
National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life;The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.
Time Frame
Through study completion,an average of 1 year
Title
Patient reported outcome (PRO)
Description
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-chemotherapy-induced peripheral neuropathy(CIPN) twenty-item scale (QLQ-CIPN20) was used to assess the quality of life.
Time Frame
Through study completion,an average of 1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female patients who will receive initial treatment, 18-70 years of age; Newly diagnosed high-risk early stage (T1c-2, N1; T2, N0) and locally advanced (T1c-2, N2-3; T3-4, N0-3) breast cancer (tumor stage II, III), in which HR+/HER2- T2, N0 patients need to be accompanied by high-risk factors (histological grade 3 or Ki67 ≥ 20%). Triple negative breast cancer(TNBC), HER2 positive (Immunohistochemical(IHC)3+; IHC 2+, FISH amplification) breast cancer, HR negative HER2 IHC 2+ and undetermined result of FISH, HR positive HER2 negative (IHC 0,1+; 2+, FISH amplification) breast cancer confirmed by pathological test. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1 The blood routine examination was basically normal (CTCAE ≤ 1) within one week before enrollment (based on the normal values of each research center laboratory). No Human Granulocyte Colony Stimulating Factor(rhGCSF) or blood transfusion/erythropoietin(EPO) or other drugs were used within 14 days prior to enrollment. White blood cell count (WBC) ≥ 4 x109 / L; Neutrophil count (ANC) > 1.5x109 / L; Platelet count (PLT) ≥ 100×109/L Hemoglobin(Hb) ≥ 100g/L. The blood biochemistry examination was basically normal (CTCAE ≤ 1) within one week before enrollment (based on the normal values of each research center laboratory) Serum total bilirubin ≤ Upper limit of normal value(ULN); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 1.5×ULN; Alkaline phosphatase ≤ 2.5×ULN; Serum creatinine ≤ 1.5×ULN. Color Doppler echocardiography left ventricular Ejection fraction (LVEF) ≥ 55% Female patients with fertility must agree to use effective contraceptive methods during the study period and within 6 months of the last study medication. The Pregnancy test (urine or serum) must be negative Be willing and able to provide written informed consent/assent for the trial. Exclusion Criteria: Primary stage IV breast cancer; Inflammatory breast cancer; Bilateral primary breast cancer (including invasive cancer and carcinoma in situ); Previous anti-cancer treatment or radiotherapy for any malignant tumor, excluding cured cervical Carcinoma in situ, skin Basal-cell carcinoma and squamous cell carcinoma. Receive any sex hormone treatment (such as contraceptives, ovarian hormone replacement therapy, etc.), except for Ovarian function suppression(OFS)fertility protection, or any hormone drugs (such as Raloxifene, tamoxifen, or other selective estrogen receptor modulators) to treat osteoporosis or prevent breast cancer; The patient has undergone major surgery unrelated to breast cancer within 4 weeks before treatment or has not yet fully recovered; Symptomatic peripheral neuropathy CTCAE 5.0 grade ≥ 2 Serious cardio cerebral Vascular disease, including but not limited to the followings: History of congestive heart failure or systolic dysfunction (LVEF<50%); Angina pectoris requiring anti angina drugs; High risk uncontrolled arrhythmias or severe conduction abnormalities, such as ventricular arrhythmias that require clinical intervention, II-III degree atrioventricular block, etc; Under resting state, the average corrected Q-T interval(QTcF) of three 12 lead electrocardiogram examinations is>470ms; Clinically significant heart valve disease with cardiac dysfunction; Hypertension that cannot be controlled; History of myocardial infarction Allergic to any component of any drug in this protocol. Those who are not suitable for using Corticosteroid. Individuals with active infections who currently require systematic anti infection treatment. History of immune deficiency disease, including positive of HIV/AIDS, or other acquired or congenital immune deficiency diseases, or having a history of organ transplantation. Who had participated in other drug intervention clinical trials within the 28 days of randomization, or who is participating in another clinical trial or is using other investigational treatments. Individuals in pregnancy (positive Pregnancy test) and lactation. Any other comorbidities that interfere with the implementation of the treatment plan, or the researcher evaluate that the subject has a history of other serious systemic diseases, or other reasons lead to the patients is unsuitable to participate in this trial.
Facility Information:
Facility Name
Cancer Hospital, Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China

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Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer

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