Trial Title:
Paclitaxel Polymeric Micelles for Injection Versus TPC on the Treatment of HER2-negative Metastatic Breast Cancer (MBC).
NCT ID:
NCT06143553
Condition:
Metastatic Breast Cancer (MBC)
Conditions: Official terms:
Breast Neoplasms
Paclitaxel
Vinorelbine
Albumin-Bound Paclitaxel
Gemcitabine
Capecitabine
Conditions: Keywords:
Paclitaxel Polymeric Micelles for Injection
Metastatic Breast Cancer (MBC)
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Paclitaxel Polymeric Micelles for Injection
Description:
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.
Arm group label:
Paclitaxel Polymeric Micelles for Injection
Intervention type:
Drug
Intervention name:
Eribulin Mesilate injection
Description:
Subjects are given 1.4 mg/m2 of Eribulin Mesilate injection on days 1 and 8 of the 21-day
cycle.
Arm group label:
The Doctor chooses the treatment（TPC）
Intervention type:
Drug
Intervention name:
Capecitabine Tablets
Description:
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).
Arm group label:
The Doctor chooses the treatment（TPC）
Intervention type:
Drug
Intervention name:
Gemcitabine Hydrochloride for Injection
Description:
Subjects are given 800-1200mg/m2 of Gemcitabine Hydrochloride for Injection on days 1, 8
and 15 of the 28-day cycle.
Arm group label:
The Doctor chooses the treatment（TPC）
Intervention type:
Drug
Intervention name:
Vinorelbine Tartrate Injection
Description:
Subjects are given 25mg/m2 of Vinorelbine Tartrate Injection every first day of the week.
Arm group label:
The Doctor chooses the treatment（TPC）
Intervention type:
Drug
Intervention name:
Paclitaxel (albumin-bound)
Description:
Subjects are given 260mg/m2 of Paclitaxel (albumin-bound) on day 1 of the 21-day
cycle,intravenous administration for more than 30 minutes.
Arm group label:
The Doctor chooses the treatment（TPC）
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Jiangsu province Hospital
Address:
City:
Nanjing
Zip:
210029
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongmei Yin
Phone:
13951842727
Email:
ym.yin@hotmail.com
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
201321
Country:
China
Status:
Recruiting
Contact:
Last name:
Jiong Wu
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
201321
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Zhang
Start date:
October 30, 2023
Completion date:
July 2025
Lead sponsor:
Agency:
Shanghai Yizhong Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Shanghai Yizhong Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06143553
