Clinical trial NCT05077449: A Study of XZP-3287 in Combination With Fulvestrant in Patients With Advanced Breast Cancer
Official title: A Phase III Study to Evaluate the Efficacy and Safety of XZP-3287 in Combination With Fulvestrant Versus Placebo Combined With Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced Breast Cancer
Keywords: XZP-3287
HR positive and Her2 negative
recurrent/metastatic breast cancer
Lead sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-14
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III clinical trial to evaluate the efficacy and safety of XZP-3287 in combination with Fulvestrant versus placebo combined with Fulvestrant in Patients who have HR positive and Her2 negative recurrent/metastatic breast cancer and have received prior endocrine therapy are eligible for study.


Eligibility criteria: Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years old;
2. Patient is in the menopausal state；
3. Pathologically-confirmed HR positive and Her2 negative Breast Cancer;
4. Locally advanced stage, recurrence or metastasis breast cancer; 4.1 Disease progression after previous endocrine therapy； 4.2 One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy;
5. At least one measurable lesion (based on RECIST v1.1) or only bone metastases;
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
7. Adequate organ and marrow function;
8. Patient of childbearing age must undergo a serum pregnancy test within 14 days before randomization, and the result is negative; patient is willing to use a medically approved high-efficiency contraceptive method during the study period and within 6 months after the last study drug treatment;
9. Patient with acute toxic reactions caused by previous anti-tumor treatments or surgical operations were alleviated to grade 0 to 1 (NCI-CTCAE v5.0), or to the level specified by the enrollment criteria;
10. Patient has signed informed consent before any trial related activities.

Exclusion Criteria:

1. Patient with visceral crisis, inflammatory breast cancer, or brain metastases, except for patient with stable brain metastases;
2. Patient had clinically significant pleural effusions, ascites effusions, or pericardial effusions in the 4 weeks before enrollment;
3. Patient who received prior treatment with mTOR inhibitors, CDK4/6 inhibitors or fulvestrant;
4. Participation in a prior treatment of major surgery, chemotherapy, radiotherapy, and any anti-tumor treatment within 14 days before enrollment；
5. Patient who participated in other clinical trials within 14 days before enrollment or within 5 half-lives of the trial drug, whichever is longer;
6. Patient used CYP3A4 potent inhibitors or potent inducers within 14 days before enrollment or within 5 half-lives of the drug, whichever is longer;
7. Patient who used bisphosphonates or RANKL inhibitors within 7 days before enrollment, patient who have started treatment during the study should not change the method of use;
8. Any other malignant tumor has been diagnosed within 3 years before randomization;
9. Patient is in the active stage of HBV, HCV or co-infected with HBV, HCV, or Patient with positive HIV antibody;
10. Patient with severe infection within 4 weeks before enrollment, or unexplained fever\> 38.5℃ during screening/before enrollment;
11. Patient with heart function impaired or clinically significant heart disease within 6 months before enrollment;
12. Cerebrovascular accident occurred within 6 months before enrollment, including history of transient ischemic attack or stroke; symptomatic pulmonary embolism;
13. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug;
14. Patient with a known hypersensitivity to any of the excipients in this study;
15. A prior history of autologous or allogeneic hematopoietic stem cell transplantation;
16. A prior history of psychotropic drug abuse or drug use;
17. Pregnant or breastfeeding;
18. The researchers considered that there were some cases that were not suitable for inclusion.

Primary outcomes:
measure: Investigator-assessed progression free survival (PFS)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: BICR-assessed progression free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Overall survival (OS)
timeFrame: Up to approximately 5 years
measure: Overall survival rate(OSR)
timeFrame: Up to approximately 5 years
measure: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Duration of response (DoR)
timeFrame: Up to approximately 24 months
measure: Disease control rate (DCR)
timeFrame: Up to approximately 24 months
measure: Clinical benefit rate (CBR)
timeFrame: Up to approximately 24 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Up to approximately 24 months
measure: Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0
timeFrame: Up to approximately 24 months
measure: Maximum Plasma Concentration [Cmax]
timeFrame: Up to approximately 4 months
measure: Time to Maximum Plasma Concentration [Tmax]
timeFrame: Up to approximately 4 months
measure: Area under the time-concentration Curve [AUC]
timeFrame: Up to approximately 4 months
Other outcomes:
measure: EORTC QLQ-C30 scale
timeFrame: Up to approximately 24 months
measure: EORTC QLQ-BR23 scale
timeFrame: Up to approximately 24 months
measure: EQ-5D-5L scale
timeFrame: Up to approximately 24 months
measure: Plasma ctDNA
timeFrame: Up to approximately 5 months
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Science
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Binghe Xu
role: PRINCIPAL_INVESTIGATOR
References: