Neoadjuvant Therapy With Weekly Utidelone Combined With Cisplatin for Patients With Breast Cancer (NeoURANIA) (NeoURANIA)

Neoadjuvant Therapy With Weekly Utidelone Combined With Cisplatin for Patients With Breast Cancer (NeoURANIA): A Multi-center, Prospective Study

This study is a prospective, multi-center, single-arm, two-cohort, exploratory study, aiming to explore the effectiveness and safety of neoadjuvant treatment with weekly utidelone combined with cisplatin in breast cancer patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: utidelone; Drug: Cisplatin; Drug: Trastuzumab; Drug: Pertuzumab

Detailed Description

Explore the effectiveness and safety of neoadjuvant treatment with weekly utidelone combined with cisplatin in high risk early, locally advanced and Inflammatory breast cancer patients.

• Study Type: Interventional
• Enrollment (Estimated): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • RenJi Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old;
2. Primary invasive breast cancer confirmed by pathology; Before neoadjuvant therapy, the primary breast lesion was larger than 2cm(cT2-T4a-d, according to the anatomical staging of AJCC 8th edition), or the clinical images of lymph nodes considered metastasis or pathologically confirmed metastasis (CN+); or patients whose primary breast lesions are more than 1cm and less than 2cm, and whose lymph nodes have not metastasized (cT1cN0) must meet one of the following conditions: hormone receptor negative, HER2 positive, or ki67 greater than 20%. If bilateral breast cancer is found at the same time, it can be admitted to the group, but it is necessary to determine which side of the lesion is to be evaluated before taking the drug;
3. According to the RECIST version 1.1 standard (see Annex I), there is at least one measurable lesion before neoadjuvant therapy;
4. The score of ECOG is 0 or 1;
5. During neoadjuvant therapy, ovarian function suppression can be given at the same time;
6. The hematological examination and blood biochemical examination should meet the following requirements: white blood cell count (WBC)≥3.0×109/L, neutrophil count (ANC)≥1.5×109/L and platelet count (PLT) ≥ 75× 109/L; Hemoglobin (HB) ≥ 80g/L; Total bilirubin (TBIL)≤1.5× upper limit of normal value (ULN), AST(sGOT), ALT(sGPT)≤2×ULN and creatinine (Cr) ≤ 1.5× ULN;
7. creatinine clearance rate ≥50mL/min(Cockcroft-Gault formula);
8. Subjects voluntarily joined the study, signed the informed consent form, and had good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. Patients during pregnancy and lactation, patients with fertility and positive baseline pregnancy test, or women of childbearing age who are unwilling to take effective contraceptive measures during the whole trial period;
2. There is distant metastasis of breast cancer confirmed by imaging or pathology before enrollment;
3. There is evidence of sensory or motor nerve diseases;
4. Severe cardiopulmonary insufficiency, severe hepatic and renal insufficiency, severe concomitant disease or active infection, including known HIV infection;
5. allergic to the research drug or its auxiliary materials;
6. Arterial/venous thrombotic events, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, occurred within 6 months before the start of the study;
7. Previous history of other malignant tumors, except the cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and the second primary malignant tumor with high 5-year recurrence-free survival rate determined by researchers;
8. According to the researcher's judgment, there are accompanying diseases (including but not limited to uncontrollable hypertension, severe diabetes, active infection, thyroid disease, etc.) that seriously endanger the patient's safety or affect the patient's completion of the study, and any other circumstances that the researcher judges that the patient is not suitable for participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2 negative breast cancer cohort; Human Epidermal Growth Factor Receptor 2 (HER2 ) negative breast cancer utidelone and cisplatin	Drug: utidelone; utidelone 50mg／m2，ivgtt，d1，8，15，22, q28d, up to 4 cycle； Other Names: UTD1; Drug: Cisplatin; cisplatin25mg/m2，ivgtt，d1，8，15；q28d, up to 4 cycle.; Other Names: DDP
Experimental: HER2 positive breast cancer cohort; Human Epidermal Growth Factor Receptor 2 (HER2 ) positive breast cancer utidelone，cisplatin，tratuzumab and pertuzumab (both Intravenous preparations or subcutaneous preparations can be used)	Drug: utidelone; utidelone 50mg／m2，ivgtt，d1，8，15，22, q28d, up to 4 cycle； Other Names: UTD1; Drug: Cisplatin; cisplatin25mg/m2，ivgtt，d1，8，15；q28d, up to 4 cycle.; Other Names: DDP; Drug: Trastuzumab; Trastuzumab 8mg/kg, ivgtt, d1, then 6mg/kg, q21d or Trastuzumab 4mg/kg, ivgtt, d1, then 2mg/kg, q7d or Trastuzumab Injection（Subcutaneous Injection）600mg，subcutaneous Injection，d1，q21d; Drug: Pertuzumab; Pertuzumab 840mg, ivgtt, d1, then 420mg, q21d or Pertuzumab/trastuzumab/hyaluronidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	ypT0/is ypN0	through surgery completion, an average of 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
breast pCR	ypT0/is	through surgery completion, an average of 16 weeks
RCB 0/I rate	ratio of patients who achieved RCB 0 or RCB I	through surgery completion, an average of 16 weeks
RCB class	RCB 0, RCB I, RCB II, RCB III	through surgery completion, an average of 16 weeks
Rate of lymph node negative	ratio of patients who achieved lymph node negative	through surgery completion, an average of 16 weeks
ORR by physical examination	ratio of patients who achieved complete response or partial response by physical examination	After completing neoadjuvant therapy before surgery, an average of 16 weeks
ORR by MRI	ratio of patients who achieved complete response or partial response by MRI	After completing neoadjuvant therapy before surgery, an average of 16 weeks
CBR by physical examination	ratio of patients who achieved complete response or partial response or stable disease by physical examination	After completing neoadjuvant therapy before surgery, an average of 16 weeks
CBR by MRI	ratio of patients who achieved complete response or partial response or stable disease by MRI	After completing neoadjuvant therapy before surgery, an average of 16 weeks
iDFS	It is defined as the time from first dose of study intervention administration to the first occurrence of ipsilateral invasive cancer recurrence, contralateral invasive breast cancer, local and/or regional invasive cancer recurrence, distant metastasis or death from any cause.	2year,3year,5year,8year,10year
EFS	It is defined as the time from first dose of study intervention administration to the first occurrence of local and/or regional recurrence, contralateral breast cancer, distant metastasis or death from any cause.	2year,3year,5year,8year,10year
DDFS	It is defined as the time from first dose of study intervention administration to the first distant metastasis or death from any cause.	2year,3year,5year,8year,10year
OS	It is defined as the time from first dose of study intervention administration to death from any cause.	2year,3year,5year,8year,10year
Quality of Life	EORTC-QLQ-C30	Through study completion，an average of 1 year
Quality of Life	EORTC-QLQ-BR23	Through study completion，an average of 1 year
Safety	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Through study completion，an average of 1 year
Combine with weekly paclitaxel with cispltin in HER2-negative and HER2-positive patients	Combine with weekly paclitaxel with cispltin in HER2-negative and HER2-positive patients	After completing neoadjuvant therapy before surgery, an average of 16 weeks

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2032

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: cisplatin; breast cancer; neoadjuvant therapy; utidelone
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Pertuzumab
• Other Study ID Numbers: SHPD009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No