Clinical trial NCT05257395: A Study of XZP-3287 in Combination With Letrozole/Anastrozole in Patients With Advanced Breast Cancer
Official title: A Phase III Study to Evaluate the Efficacy and Safety of XZP-3287 Combined With Letrozole/Anastrozole Versus Placebo Combined With Letrozole/Anastrozole 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 Her2 negative recurrent/metastatic breast cancer
Lead sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-25
Enrollment: 397
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 designed to evaluate the efficacy and safety of XZP-3287 in combination with Letrozole/Anastrozole versus placebo in combination with Letrozole/Anastrozole in patients with HR-positive and HER2-negative recurrent/metastatic breast cancer who have not received systemic anticancer therapy.


Eligibility criteria: Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years old;
2. Patient is in the menopausal state；
3. Histologically or cytologically confirmed locally advanced, recurrent or metastatic breast cancer, which was pathologically confirmed to be HR-positive and HER2-negative;
4. Evidence of locally advanced, recurrent, or metastatic disease that is not amenable to curative surgical resection or radiation therapy and is not clinically amenable to chemotherapy;
5. No prior systemic anticancer therapy for locally advanced, recurrent, or metastatic disease;
6. At least one measurable lesion (based on RECIST v1.1) or only bone metastases;
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
8. Adequate organ and marrow function;
9. Patient of childbearing age must undergo a serum pregnancy test within 7 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;
10. 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;
11. Patient has signed informed consent before any trial related activities.

Exclusion Criteria:

1. Patients with disease recurrence or metastasis at or within 12 months after previous neoadjuvant or adjuvant therapy with endocrine drugs;
2. Patient with visceral crisis or brain metastases, except for patient with stable brain metastases;
3. Patient had clinically significant pleural effusions, ascites effusions, or pericardial effusions in the 4 weeks before enrollment;
4. Patient who received prior treatment with mTOR inhibitors or CDK4/6 inhibitors ;
5. Participation in a prior treatment of major surgery, chemotherapy, radiotherapy, and any anti-tumor treatment within 14 days before enrollment；
6. Patient who participated in other clinical trials within 14 days before enrollment or within 5 half-lives of the trial drug, whichever is longer;
7. Patient used CYP3A4 potent inhibitors or potent inducers within 14 days before enrollment or within 5 half-lives of the drug, whichever is longer;
8. Initiation of bisphosphonates or RANKL inhibitors within 7 days before enrollment, and subjects who have initiated treatment \> 7 days before enrollment should not change the method of use;
9. Any other malignant tumor has been diagnosed within 5 years before randomization;
10. Patient is in the active stage of HBV, HCV or co-infected with HBV, HCV, or Patient with positive HIV antibody;
11. Patient with severe infection within 4 weeks before enrollment, or unexplained fever\> 38.3℃ during screening/before enrollment;
12. Patient with heart function impaired or clinically significant heart disease within 6 months before enrollment;
13. Cerebrovascular accident occurred within 6 months before enrollment, including history of transient ischemic attack or stroke; pulmonary embolism;
14. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug;
15. Patient with a known hypersensitivity to any of the excipients in this study;
16. A prior history of autologous or allogeneic hematopoietic stem cell transplantation;
17. A prior history of psychotropic drug abuse or drug use;
18. Nursing Mothers;
19. 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: Time to Deterioration（TTD）
timeFrame: Up to approximately 24 months
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
Locations:
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
Study officials:
affiliation: The Second Affiliated Hospital of Harbin Medical University
name: Qingyuan Zhang
role: PRINCIPAL_INVESTIGATOR
References: