Bortezomib Plus Cisplatin in Recurrent or Metastatic Breast Cancer

Phase 1

Recruiting

• Conditions: Metastatic Breast Cancer; Recurrent Breast Cancer
• Interventions: Drug: Bortezomib (B); Drug: Cisplatin (CDDP)

• Registration Number: NCT06900647
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This a phase 1 study to evaluate the safety and preliminary efficacy of cisplatin combined with bortezomib in patients with recurrent or metastatic breast cancer.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-01-01
• Status Verified: 2025-03
• Study First Submitted: 2025-03-16
• Study First Submitted QC: 2025-03-21
• Last Update Submitted: 2025-03-27
• Study First Posted: 2025-03-28
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

1. Women aged 18 years and above with pathologically confirmed recurrent or metastatic advanced breast cancer ;
2. The patient has tumor specimens (formalin-fixed, paraffin-embedded or fresh pre-treated recurrent tumor tissue);
3. Patients who have failed standard treatment in the late stage;
4. At least one measurable lesion;
5. ECOG PS : 0-2 points;
6. Estimated survival period ≥12 weeks;
7. The function level of major organs meets the following standards:

1. The blood routine examination standards must meet: ANC ≥1.5×109/L, PLT ≥75×109/L, Hb ≥85g/L (no blood transfusion and blood products within 14 days, no use of G-CSF and other hematopoietic stimulating factors for correction) 2) Biochemical examinations must meet the following standards: TBIL <1.5×ULN, ALT, AST <2.5×ULN, ALT, AST <5×ULN for patients with liver metastasis, BUN and Cr ≤1×ULN or endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula); 8. Women of childbearing age must have taken reliable contraceptive measures, or have undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and are willing to use appropriate contraceptive methods during the trial and 8 weeks after the last administration of the trial drug.

9. The subjects voluntarily join this study, have good compliance, and cooperate with follow-up.

Exclusion Criteria

Any of the following will be considered as meeting the exclusion criteria of the study:

1. Patients with acute active hepatitis B or acute active hepatitis C;
2. Any serious underlying disease, comorbidity and active infection
3. Currently receiving other anti-tumor treatments;
4. History of epilepsy or epileptic-induced condition;
5. Patients who are pregnant or breastfeeding;
6. Those with poor compliance or unable to undergo normal follow-up;
7. Allergic to study drugs;
8. Patients diagnosed with other malignant tumors within 5 years, except for the following: surgically resected non-melanoma skin cancer, adequately treated cervical carcinoma in situ, surgically radically treated ductal carcinoma in situ, or malignant tumors diagnosed 2 years ago with no current evidence of disease and untreated ≤ 2 years before randomization;
9. The researcher determines other situations that may affect the conduct of the clinical study and the determination of the study results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose level 1	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 1	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 2	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 2	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 3	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 3	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.
Dose level 4	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.
Dose level 4	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.
Dose level 5	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.
Dose level 5	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.
Dose level 6	Bortezomib (B)	In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.
Dose level 6	Cisplatin (CDDP)	In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities (DLTs)	Within 28 days after the first dose.	The DLT assessment period is from day 1 to day 21 of the subject's first dose plus 24 hours after the second dose, that is, 22 days.; Each dose group must first enroll 3 subjects. If no DLT occurs in the first cycle (within 28 days after the first dose), the dose will be increased to the next cohort; if 1 subject develops DLT, 3 subjects will be added to the cohort, and if no DLT occurs in the last 3 subjects, the dose will be increased to the next dose. If 2 or more subjects in 3 or 6 subjects in a dose group develop DLT, the dose escalation will be stopped, and the previous dose of the dose will be the MTD. DLT is defined as a treatment-related adverse event of Grade 3 or higher, based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Maximum Tolerated Dose (MTD)	Within 28 days after the first dose.	If 2 or more subjects in 3 or 6 subjects in a dose group develop DLT, the dose escalation will be stopped , and the previous dose of the dose will be the MTD. If the MTD is not reached in this trial, the researchers will discuss whether to continue the subsequent escalation trial.

Secondary Outcome Measures

Name	Time	Method
Progression- free survival ( PFS )	Within approximately 48 months.	PFS assessed by investigators according to RECIST version 1.1 criteria.
Objective Response Rate (ORR)	Within approximately 48 months	ORR assessed by investigators according to RECIST version 1.1 criteria.
Disease Control Rate (DCR)	Within approximately 48 months	DCR assessed by investigators according to RECIST version 1.1 criteria.
Area Under the Curve (AUC)	Blood samples for PK analysis were collected within 60 minutes before dosing, at 0.5, 2, 6, 24, 72 hours, and on days 8, 15, and 22 after the start of dosing.	The area under the plasma concentration-time curve (AUC) will be measured to evaluate the systemic exposure of bortezomib and cisplatin. Blood samples will be collected at specified time points to calculate AUC using non-compartmental analysis.
Maximum Plasma Concentration (Cmax)	Blood samples for PK analysis were collected within 60 minutes before dosing, at 0.5, 2, 6, 24, 72 hours, and on days 8, 15, and 22 after the start of dosing.	The maximum observed plasma concentration (Cmax) of bortezomib and cisplatin will be determined from the collected blood samples. Cmax reflects the peak concentration of the drug in plasma after administration.
Time to Maximum Plasma Concentration (Tmax)	Blood samples for PK analysis were collected within 60 minutes before dosing, at 0.5, 2, 6, 24, 72 hours, and on days 8, 15, and 22 after the start of dosing.	The time to reach the maximum plasma concentration (Tmax) will be assessed for bortezomib and cisplatin. Tmax will be determined directly from the plasma concentration-time data.
Half-Life (T1/2)	Blood samples for PK analysis were collected within 60 minutes before dosing, at 0.5, 2, 6, 24, 72 hours, and on days 8, 15, and 22 after the start of dosing.	The terminal elimination half-life (T1/2) of bortezomib and cisplatin will be calculated using non-compartmental analysis. T1/2 represents the time required for the plasma concentration of the drug to decrease by 50%.

Trial Locations

Locations (1)

Sun Yat-Sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China