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Trial Title:
Randomized, Open, Controlled, Multicenter Phase III Clinical Study of Fluzoparib in Combination With Apatinib Versus Investigator-Selected Chemotherapy for HRD-Positive/HER2-negative Advanced Breast Cancer
NCT ID:
NCT06255392
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Paclitaxel
Vinorelbine
Gemcitabine
Capecitabine
Apatinib
Fluzoparib
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fluzoparib
Description:
Fluzoparib capsules appropriate dose oral, each treatment cycle defined as 3 weeks (21
days).
Arm group label:
Fluzoparib Combined With Apatinib
Intervention type:
Drug
Intervention name:
Apatinib Mesylate
Description:
Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).
Arm group label:
Fluzoparib Combined With Apatinib
Intervention type:
Drug
Intervention name:
Capecitabine tablets
Description:
Capecitabine tablets, reasonable dosage with reference to guidelines, each treatment
cycle defined as 3 weeks (21 days).
Arm group label:
Chemotherapy selected by the investigator
Intervention type:
Drug
Intervention name:
Vinorelbine Tartrate Oral
Description:
For the first three courses: reasonable dosage with reference to guidelines. After 3
courses of medication, it is recommended to increase the dose of vinorelbine tartrate
once a week. Each treatment cycle defined as 3 weeks (21 days).
Arm group label:
Chemotherapy selected by the investigator
Intervention type:
Drug
Intervention name:
Eribulin mesylate injection
Description:
Eribulin, reasonable dosage with reference to guidelines, each treatment cycle defined as
3 weeks (21 days).
Arm group label:
Chemotherapy selected by the investigator
Intervention type:
Drug
Intervention name:
Gemcitabine Hydrochloride
Description:
Gemcitabine, reasonable dosage with reference to guidelines, each treatment cycle defined
as 3 weeks (21 days).
Arm group label:
Chemotherapy selected by the investigator
Intervention type:
Drug
Intervention name:
Paclitaxel-albumin
Description:
Paclitaxel-albumin, reasonable dosage with reference to guidelines, each treatment cycle
defined as 3 weeks (21 days).
Arm group label:
Chemotherapy selected by the investigator
Summary:
This study develops a new therapeutic approach for HER2-negative advanced breast cancer
patients without precise treatment targets. The trial aims at extending the combination
target therapy involving PARP inhibitors and anti-angiogenesis from only BRCA mutation
carriers to all patients with homologous recombination repair defects (HRD-positive). The
phase III randomized clinical study will investigate the effectiveness of the combination
therapy of PARP inhibitor "fludzoparib" and anti-angiogenic "apatinib" in treating
HRD-positive/HER2-negative advanced breast cancers.
Detailed description:
Breast cancer is the most prevalent malignant tumor in the world, and 30% of breast
cancer patients will enter the advanced stage due to treatment failure. 80% of these
patients have HER2-negative subtype breast cancer, which has not yet been found the
similar target as HER2, with the median survival time of only 6-20 months. In the past,
ovarian cancer patients faced the dilemma of poor survival due to the lack of precise
targeted therapy. However, through a series of clinical studies, experts in the field of
ovarian cancer have successfully expanded the indications of PARP inhibitor-based
combination targeted therapy from the small population of BRCA mutation(20%) to the large
population of HRD-positive (Homologous recombination deficiency) (50%), which has
significantly prolonged the survival time of patients. Because causes other than BRCA
mutations can also cause tumor cells to be "HRD" and thus sensitive to PARP inhibitors,
so that HRD-positive patients are likely to benefit. The HRD-positive profile of nearly
50% of the patients could be a potential beneficiary of PARP inhibitor-based targeted
therapy. The synergistic effect of PARP inhibitor and anti-angiogenic combination therapy
has already been confirmed in preliminary cellular experiments and clinical studies
related to ovarian cancer. Further cell-based experiments and preclinical studies have
also confirmed the feasibility of the combination targeted therapy in the
HRD-positive/HER2-negative subtype of breast cancer. Therefore, we intend to further
validate the efficacy and safety of the PARP inhibitor fluazoparib in combination with
the antiangiogenic abatinib in a Phase III, randomized, controlled clinical study, in
order to provide HRD-positive/HER2-negative breast cancer patients with a better choice
of precision targeted therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult female patients (age 18-70 years) with metastatic breast cancer confirmed by
pathology or imaging;
2. Pathological diagnosis of HER-2 was negative (definition: immunohistochemical
results were 0、+ or ++ and in situ hybridization results were negative);
3. Patient tested positive for HRD (defined by: BRCA 1 / 2 mutation, or HRD score is ≥
42);
4. HR+/HER2- patients were required to have received endocrine therapy during the
metastatic phase;
5. ECOG physical status score ≤ 2 and expected survival of not less than 3 months;
6. According to RECIST 1.1, patients with at least one target lesion or simple bone
metastasis can be evaluated;
7. Prior treatment-related toxicity should be reduced to NCI CTCAE (version 5.0) ≤ 1
degree (except for hair loss or other toxicity which is considered as no risk to
patient's safety according to the investigator's judgment) 8）LVEF≥50%；
8. Sufficient functional reserve of bone marrow
1. White blood cell count (WBC) ≥ 3.0 × 10 ^ 9 / L,
2. Neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L,
3. Platelet count (PLT) ≥ 100 × 10 ^ 9 / L
9. Previous treatment-related toxicity should be relieved as NCI CTCAE (version 5.0) ≤
1 degree, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), alanine
aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), serum
creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min;
10. Left ventricular ejection fraction (LVEF) ≥ 55%, QTcF(Fridericia correction) ≤ 470
ms.
11. Be able to understand the research process, volunteer to participate in the study,
and sign informed consent.
Exclusion Criteria:
1. HR+/HER2- MBC patients with no prior endocrine therapy;
2. No treatment for metastatic breast cancer was received;
3. Patients who are known to be allergic to active or other components of the study
drug.
4. They received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before
enrollment, or were participating in any clinical trials of intervention drugs;
5. Pregnant or lactating women, women of childbearing age who refused to take effective
contraceptive measures during the study period.
6. Any other situation in which the researcher considers that the patient is not
suitable for the study may interfere with the concomitant diseases or conditions
involved in the study, or there are any serious medical barriers that may affect the
safety of the subjects (e.g., uncontrollable heart disease, hypertension, active or
uncontrollable infection, active hepatitis B virus infection)
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat Sen Memorial Hospital，Sun Yat sen University
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Start date:
February 2024
Completion date:
March 2031
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06255392
