Efficacy and Safety of Paclitaxel Polymeric Micelles for Injection in the Treatment of Metastatic Breast Cancer

NCT06143553 | Recruiting Phase 3 DMC

• 1 other identifier: SHYZ-ZSCJS-RXⅢ-01
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 3

Brief Summary

This multicenter, randomized, open, parallel positive control study compares the clinical efficacy and safety of paclitaxel polymeric micelles for injection with TPC in HER2- MBC subjects who have failed ≥2 to≤4 previous chemotherapy regimens. Treatment Protocol: Subjects are randomized into paclitaxel polymeric micelles for injection group and the Physician's Choice (TPC) group by the proportion of 1:1. Randomization is stratified according to three factors: number of lines of previous treatment for metastatic disease (2 or 3/4 lines), receptor status (triple-negative, non-triple-negative), and visceral metastasis (yes/no). Progression-free survival (PFS) is the main efficacy indicator in this study. Treatment Group: Subjects are given paclitaxel polymeric micelles for injection, three weeks constitutes one cycle of treatment. Control Group: Physician's Choice Group, subjects are given Eribulin Mesilate injection; or capecitabine tablets; or gemcitabine hydrochloride for injection; or vinorelbine tartrate injection; or paclitaxel (albumin-bound). Three or four weeks constitutes one cycle of treatment. If subject does not develop disease progression after 6 cycles of dosing, the subject continues treatment until disease progression (RECIST 1.1) or develops an intolerable toxicity, initiation of a new anti-cancer drug, withdrawal from the study, death, or loss of follow-up. Superiority design is used in this study, progression-free survival (PFS) is the main efficacy indicator. Assuming α = 0.0249(unilateral, adjusted test level), power=80%, the median PFS of the treatment group is 6.0 months, the median PFS of the control group is 3.7 months, the enrollment period is 12 months, and the study period is 24 months. Using PASS (version 11.0) for calculation, a total of 152 subjects (76 in each group) are required to meet the statistical significance between the treatment group and the control group. In consideration of case expulsion, enlarged by 10%, a total of 168 subjects (84 in each group) are required.

Conditions

Metastatic Breast Cancer (MBC)

Keywords

Paclitaxel Polymeric Micelles for Injection; Metastatic Breast Cancer (MBC); human epidermal growth factor receptor 2-negative (HER2-)

Outcome Measures

Primary Outcomes (1)

• Progression-Free-Survival

  PFS(Progression-Free-Survival) was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first

  Randomization to measured PD or date of death from any cause（up to 24 months)

Secondary Outcomes (4)

• Objective response rate

  Baseline to measured PD（up to 24 months)

• Overall survival

  Randomization to date of death from any cause（up to 24 months)

• Disease Control Rate

  Baseline to measured PD（up to 24 months)

• Incidence of adverse events

  up to 24 months

Study Arms (2)

Paclitaxel Polymeric Micelles for Injection

EXPERIMENTAL

300mg/m2 of Paclitaxel Polymeric Micelles for Injection is intravenously administrated for ≥ 3 hours without special infusion device. The frequency of administration is once every 3 weeks (Q3W), and 3 weeks constitutes a treatment cycle.

Drug: Paclitaxel Polymeric Micelles for Injection

The Doctor chooses the treatment（TPC）

ACTIVE COMPARATOR

Control Group：The Doctor chooses the treatment（TPC）：Eribulin Mesilate injection；Capecitabine Tablets；Gemcitabine Hydrochloride for Injection；Vinorelbine Tartrate Injection；Paclitaxel (albumin-bound). Eribulin Mesilate injection：on days 1 and 8 of the 21-day cycle, 1.4 mg/m2 , intravenous administration; Capecitabine Tablets: On days 1 to 14 of the 21-day cycle, 1000-1250mg/m2，oral administration, twice a day (once in the morning and once in the evening; Total daily dose 2000-2500mg/m2); Gemcitabine Hydrochloride for Injection: On days 1, 8 and 15 of the 28-day cycle, 800-1200mg/m2, intravenous administration; Vinorelbine Tartrate Injection: Every first day of the week, 25mg/m2，intravenous administration; Paclitaxel (albumin-bound): On day 1 of the 21-day cycle, 260mg/m2，intravenous administration for more than 30 minutes. Three weeks constituted one course of treatment.

Drug: Eribulin Mesilate injection; Drug: Capecitabine Tablets; Drug: Gemcitabine Hydrochloride for Injection; Drug: Vinorelbine Tartrate Injection; Drug: Paclitaxel (albumin-bound)

Interventions

Paclitaxel Polymeric Micelles for Injection DRUG

Subjects are given 300 mg/m2 of Paclitaxel Polymeric Micelles for Injection without special infusion device,intravenously administrated for ≥ 3 hours.Three weeks constituted one course of treatment.

Paclitaxel Polymeric Micelles for Injection

Eribulin Mesilate injection DRUG

Subjects are given 1.4 mg/m2 of Eribulin Mesilate injection on days 1 and 8 of the 21-day cycle.

The Doctor chooses the treatment（TPC）

Capecitabine Tablets DRUG

Subjects are given 1000-1250mg/m2 of Capecitabine Tablets on days 1 to 14 of the 21-day cycle ,and twice a day (once in the morning and once in the evening; Total daily dose 2000-2500mg/m2).

The Doctor chooses the treatment（TPC）

Gemcitabine Hydrochloride for Injection DRUG

Subjects are given 800-1200mg/m2 of Gemcitabine Hydrochloride for Injection on days 1, 8 and 15 of the 28-day cycle.

The Doctor chooses the treatment（TPC）

Vinorelbine Tartrate Injection DRUG

Subjects are given 25mg/m2 of Vinorelbine Tartrate Injection every first day of the week.

The Doctor chooses the treatment（TPC）

Paclitaxel (albumin-bound) DRUG

Subjects are given 260mg/m2 of Paclitaxel (albumin-bound) on day 1 of the 21-day cycle,intravenous administration for more than 30 minutes.

The Doctor chooses the treatment（TPC）

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must meet all the following criteria:
• Male or female 18 years and older;
• Understand the purpose, benefits and risks of this clinical trial, voluntarily participate in and sign the written informed consent;
• The Eastern Cooperative Oncology Group (ECOG)performance status is 0 or 1;
• Histologically or cytologically confirmed (local laboratory) HER2-metastatic breast cancer from recently acquired or newly acquired tumor biopsies from locally-relapsed or metastatic sites (HER2- is defined as a standard immunohistochemical (IHC) test result of 0 or 1+; Or the IHC test result is 2+ and the ISH test result is negative including FISH/CISH/SISH)；
• Archival slides or newly obtained biopsy slides from metastatic or recurrent sites are available (Note: Bone lesion biopsy is not accepted);
• Subjects are eligible to receive one the chemotherapy regimens in the TPC group；
• According to RECIST 1.1, subjects with measurable lesions on contrast-enhanced CT or MRI (≥10mm in the major dimension on CT or MRI scan, and ≥15mm in the minor dimension of lymph nodes); Subjects with unmeasurable skeletal lesions only are not accepted；
• Functions of major organs such as heart, lung, liver and kidney are basically normal；
• Blood routine examination meets the following criteria (No blood transfusions, blood products, granulocyte colony-stimulating factor, or other hematopoietic growth factors were used within 7 days before the blood routine test)：
• : White blood cell count ≥3.0x109/L; Neutrophil count ≥1.5x109/L；
• : Platelet count ≥100×109/L;
• ：Hemoglobin≥90g/L;
• : If subjects receive blood component transfusion (red blood cells, platelets, etc.) during the screening period, blood routine test should be performed again at an interval of 1 week to meet the above criteria before continuing screening.
• Blood biochemical examination must meet the following criteria:

You may not qualify if:

• Known allergy or intolerance to either study treatment or any excipients；
• Previous use of antibody-drug conjugate (ADC) with anti-microtubule inhibitor as payload drug are not eligible;
• Primary brain tumors or central nervous system metastases (including leptomeningeal metastases), except for single brain metastases strictly controlled asymptomatic subjects; Subjects with intracranial hypertension or neuropsychiatric symptoms after treatment of central nervous system tumors;
• Subjects with acute or chronic infections that have not been eliminated, or subjects with other serious diseases at the same time;
• Subjects have other malignant tumors within 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• Subjects with a known history of clinically significant active chronic obstructive pulmonary disease or other moderate to severe chronic respiratory disease within 6 months before enrollment;
• Subjects with active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease), clinically significant gastrointestinal (GI) bleeding, intestinal obstruction, or GI perforation within 6 months before enrollment;
• Subjects with active hepatitis, or liver metastasis is more than 3/4 of the whole liver;
• Subjects with third-space effusions (e.g., moderate-to-massive pleural effusion, moderate-to-massive pericardial effusion, ascites) that cannot be controlled by drainage or other means; Subjects with a small amount of pleural effusion without clinical symptoms and no need for clinical intervention should be strictly controlled before enrollment;
• Subjects with mental illness or disorder, poor compliance, or inability to cooperate, or describe treatment responses;
• Subjects who cannot tolerate chemotherapy due to severe organic disease or major organ failure, such as decompensated heart and lung failure;
• Subjects with bleeding disorders;
• Subjects with organ transplant;
• Subjects with bad drug addicts, long-term alcoholics, infectious diseases such as AIDS;
• Subjects on long-term use of adrenocortical hormones or immunosuppressants;

Sponsors & Collaborators

• Shanghai Yizhong Pharmaceutical Co., Ltd.: lead

Study Sites (3)

Jiangsu province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Injections; eribulin; Capecitabine; Gemcitabine; Vinorelbine; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Economics; Health Care Economics and Organizations

Study Officials

• Yongmei Yin

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

• Jiong Wu

  Fudan University

  PRINCIPAL INVESTIGATOR

• Jian Zhang

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoya Wang

CONTACT

15601735965; 15601735965@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2023
• First Posted: November 22, 2023
• Study Start: September 25, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 29, 2024

Record last verified: 2024-08

Locations

CN (3)