Overview

Paclitaxel Polymeric Micelles for Injection Versus TPC on the Treatment of HER2-negative Metastatic Breast Cancer (MBC).

Status:
Recruiting
Trial end date:
2025-07-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Shanghai Yizhong Pharmaceutical Co., Ltd.
Treatments:
Albumin-Bound Paclitaxel
Capecitabine
Gemcitabine
Paclitaxel
Vinorelbine
Criteria
Inclusion Criteria:

- Eligible subjects must meet all the following criteria:

1. Male or female 18 years and older;

2. Understand the purpose, benefits and risks of this clinical trial, voluntarily
participate in and sign the written informed consent;

3. The Eastern Cooperative Oncology Group (ECOG)performance status is 0 or 1;

4. 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);

5. Archival slides or newly obtained biopsy slides from metastatic or recurrent
sites are available (Note: Bone lesion biopsy is not accepted);

6. Subjects who are refractory or relapsed after ≥2 and ≤4 prior systemic
chemotherapy regimens or antibody-drug conjugates (ADC) for MBC are
eligible(Subjects were eligible for inclusion if their previous chemotherapy
regimen included taxanes or not; Subjects using taxanes for adjuvant or
neoadjuvant chemotherapy more than 6 months after the treatment, and Subjects
using taxanes for advanced-stage treatment more than 3 months after the
treatment, with recurrence or metastasis are eligible.) Adjuvant or neoadjuvant
chemotherapy for early-stage disease can be considered as one of the required
prior chemotherapy regimens if unresectable, locally advanced, or metastatic
disease develops within 12 months after completion of the regimen.( Note:
Therapies for bone metastases (e.g., bisphosphonates, denosumab, etc.) are not
considered prior systemic chemotherapy for advanced disease.);

7. Subjects are eligible to receive one the chemotherapy regimens in the TPC group;

8. 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;

9. Functions of major organs such as heart, lung, liver and kidney are basically
normal;

10. 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):

1. : White blood cell count ≥3.0x109/L; Neutrophil count ≥1.5x109/L;

2. : Platelet count ≥100×109/L;

3. :Hemoglobin≥90g/L;

4. : 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.

11. Blood biochemical examination must meet the following criteria:

1. : Total bilirubin ≤1.5 times the upper limit of normal (ULN);

2. : AST, ALT, or ALP≤2.5 times ULN (ALT, AST, or ALP≤ 5×ULN for subjects with
liver metastases, and ALP≤10×ULN for subjects with bone metastases);

3. : Creatinine clearance (calculated using Cockcroft-Gault formula) ≥50
ml/min.

12. Subjects have no symptoms of cardiac dysfunction (NYHA class ≤II) at baseline and
no significant or clinically insignificant ECG abnormalities;

13. Subjects have good compliance and voluntarily comply with the clinical trial
protocol during the study, followed up by the investigators;

14. All women of childbearing age, men of childbearing potential, or their spouses
who have no plans to have children or donate sperm during the entire trial period
and up to 6 months after the last dose of medication, or who voluntarily used
effective contraception; Women of childbearing age who have a negative
blood/urine pregnancy test within 7 days prior to enrollment.

Exclusion Criteria:

- Subjects meet the following criteria are not eligible for inclusion:

1. Known allergy or intolerance to either study treatment or any excipients;

2. Previous use of antibody-drug conjugate (ADC) with anti-microtubule inhibitor as
payload drug are not eligible;

3. 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;

4. Subjects with acute or chronic infections that have not been eliminated, or
subjects with other serious diseases at the same time;

5. Subjects have other malignant tumors within 5 years (except cured basal cell
carcinoma of the skin and carcinoma in situ of the cervix);

6. 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;

7. 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;

8. Subjects with active hepatitis, or liver metastasis is more than 3/4 of the whole
liver;

9. 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;

10. Subjects with mental illness or disorder, poor compliance, or inability to
cooperate, or describe treatment responses;

11. Subjects who cannot tolerate chemotherapy due to severe organic disease or major
organ failure, such as decompensated heart and lung failure;

12. Subjects with bleeding disorders;

13. Subjects with organ transplant;

14. Subjects with bad drug addicts, long-term alcoholics, infectious diseases such as
AIDS;

15. Subjects on long-term use of adrenocortical hormones or immunosuppressants;

16. Subjects who received vaccines (including live and live attenuated vaccines) such
as measles, mumps, rubella, varicella, yellow fever, rabies, BCG and typhoid
(oral) vaccines within 4 weeks before enrollment, or are scheduled to receive
vaccines during the study period; Subjects who received all types of COVID-19
vaccines within two weeks before enrollment;

17. Subjects who received antineoplastic drugs (including but not limited to
chemotherapy, hormonal therapy, immunotherapy, antibody therapy, radiotherapy,
surgery (except diagnostic biopsy), etc.) within 2 weeks before enrollment or who
still have grade ≥2 toxicity from previous antineoplastic therapy (except
alopecia and grade ≤2 neurotoxicity caused by platinum) at enrollment;

18. Subjects with active hepatitis B or C (previous history of hepatitis B infection,
with or without drug control, HBV DNA≥1×104 copies or ≥2000 IU/mL; Hepatitis C
infection, HCV RNA≥15IU/mL); Or HIV antibody positive (testing is not necessary
if there is no clinical evidence to suggest possible HIV infection);

19. Subjects are considered not able to complete the trial or otherwise unfit to
participate in the study by the investigators.