Bortezomib Plus Cisplatin in Recurrent or Metastatic Breast Cancer

NCT06900647 | Recruiting Phase 1 DMC

• 1 other identifier: 2024-FXY-300
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer; Recurrent Breast Cancer

Keywords

Breast cancer; Bortezomib; Cisplatin

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLTs)

  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.

  Within 28 days after the first dose.

• Maximum Tolerated Dose (MTD)

  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.

  Within 28 days after the first dose.

Secondary Outcomes (7)

• Progression- free survival ( PFS )

  Within approximately 48 months.

• Objective Response Rate (ORR)

  Within approximately 48 months

• Disease Control Rate (DCR)

  Within approximately 48 months

• 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.

• 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.

Study Arms (6)

Dose level 1

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.

Drug: Bortezomib (B); Drug: Cisplatin (CDDP)

Dose level 2

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.

Drug: Cisplatin (CDDP); Drug: Bortezomib (B)

Dose level 3

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 50mg/m2 cisplatin.

Drug: Cisplatin (CDDP); Drug: Bortezomib (B)

Dose level 4

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.3m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.

Drug: Bortezomib (B); Drug: Cisplatin (CDDP)

Dose level 5

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.5m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.

Drug: Bortezomib (B); Drug: Cisplatin (CDDP)

Dose level 6

EXPERIMENTAL

In this dose level, all subjects will receive a dose of 1.7m/m2 bortezomib combined with a dose of 75mg/m2 cisplatin.

Drug: Bortezomib (B); Drug: Cisplatin (CDDP)

Interventions

Bortezomib (B) DRUG

1.3mg/m2, IV, D1, D4, D8 and D11, every 3 weeks

Dose level 1; Dose level 4

Cisplatin (CDDP) DRUG

50mg/m2, IV, D1-3, every 3 weeks

Dose level 1; Dose level 2; Dose level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 18 years and above with pathologically confirmed recurrent or metastatic advanced breast cancer ;
• The patient has tumor specimens (formalin-fixed, paraffin-embedded or fresh pre-treated recurrent tumor tissue);
• Patients who have failed standard treatment in the late stage;
• At least one measurable lesion;
• ECOG PS : 0-2 points;
• Estimated survival period ≥12 weeks;
• The function level of major organs meets the following standards:
• \) 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.
• \. The subjects voluntarily join this study, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Patients with acute active hepatitis B or acute active hepatitis C;
• Any serious underlying disease, comorbidity and active infection
• Currently receiving other anti-tumor treatments;
• History of epilepsy or epileptic-induced condition;
• Patients who are pregnant or breastfeeding;
• Those with poor compliance or unable to undergo normal follow-up;
• Allergic to study drugs;
• 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;
• The researcher determines other situations that may affect the conduct of the clinical study and the determination of the study results.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (17)

• Shao F, Lyu X, Miao K, Xie L, Wang H, Xiao H, Li J, Chen Q, Ding R, Chen P, Xing F, Zhang X, Luo GH, Zhu W, Cheng G, Lon NW, Martin SE, Wang G, Chen G, Dai Y, Deng CX. Enhanced Protein Damage Clearance Induces Broad Drug Resistance in Multitype of Cancers Revealed by an Evolution Drug-Resistant Model and Genome-Wide siRNA Screening. Adv Sci (Weinh). 2020 Oct 11;7(23):2001914. doi: 10.1002/advs.202001914. eCollection 2020 Dec.

  PMID: 33304752 BACKGROUND

• Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017 Jul;14(7):417-433. doi: 10.1038/nrclinonc.2016.206. Epub 2017 Jan 24.

  PMID: 28117417 BACKGROUND

• Irvin WJ Jr, Orlowski RZ, Chiu WK, Carey LA, Collichio FA, Bernard PS, Stijleman IJ, Perou C, Ivanova A, Dees EC. Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer. Clin Breast Cancer. 2010 Dec 1;10(6):465-70. doi: 10.3816/CBC.2010.n.061.

  PMID: 21147690 BACKGROUND

• Engel RH, Brown JA, Von Roenn JH, O'Regan RM, Bergan R, Badve S, Rademaker A, Gradishar WJ. A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience. Cancer Invest. 2007 Dec;25(8):733-7. doi: 10.1080/07357900701506573. Epub 2007 Oct 18.

  PMID: 17952740 BACKGROUND

• Thaler S, Thiede G, Hengstler JG, Schad A, Schmidt M, Sleeman JP. The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer. Int J Cancer. 2015 Aug 1;137(3):686-97. doi: 10.1002/ijc.29404. Epub 2015 Jan 8.

  PMID: 25530422 BACKGROUND

• Mack PC, Davies AM, Lara PN, Gumerlock PH, Gandara DR. Integration of the proteasome inhibitor PS-341 (Velcade) into the therapeutic approach to lung cancer. Lung Cancer. 2003 Aug;41 Suppl 1:S89-96. doi: 10.1016/s0169-5002(03)00149-1.

  PMID: 12867067 BACKGROUND

• Ikezoe T, Yang Y, Saito T, Koeffler HP, Taguchi H. Proteasome inhibitor PS-341 down-regulates prostate-specific antigen (PSA) and induces growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells. Cancer Sci. 2004 Mar;95(3):271-5. doi: 10.1111/j.1349-7006.2004.tb02215.x.

  PMID: 15016328 BACKGROUND

• Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22.

  PMID: 10363983 BACKGROUND

• Pharoah PD, Day NE, Caldas C. Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer. 1999 Aug;80(12):1968-73. doi: 10.1038/sj.bjc.6690628.

  PMID: 10471047 BACKGROUND

• Osin PP, Lakhani SR. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis. Breast Cancer Res. 1999;1(1):36-40. doi: 10.1186/bcr11. Epub 1999 Oct 27.

  PMID: 11250681 BACKGROUND

• Orlowski RZ, Dees EC. The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer. Breast Cancer Res. 2003;5(1):1-7. doi: 10.1186/bcr460. Epub 2002 Aug 14.

  PMID: 12559038 BACKGROUND

• Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005 Jun 1;5(1):18. doi: 10.1186/1475-2867-5-18.

  PMID: 15929791 BACKGROUND

• Lenz HJ. Clinical update: proteasome inhibitors in solid tumors. Cancer Treat Rev. 2003 May;29 Suppl 1:41-8. doi: 10.1016/s0305-7372(03)00082-3.

  PMID: 12738242 BACKGROUND

• Cusack JC. Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev. 2003 May;29 Suppl 1:21-31. doi: 10.1016/s0305-7372(03)00079-3.

  PMID: 12738240 BACKGROUND

• Adams J. Development of the proteasome inhibitor PS-341. Oncologist. 2002;7(1):9-16. doi: 10.1634/theoncologist.7-1-9.

  PMID: 11854543 BACKGROUND

• Kane RC, Farrell AT, Sridhara R, Pazdur R. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res. 2006 May 15;12(10):2955-60. doi: 10.1158/1078-0432.CCR-06-0170.

  PMID: 16707588 BACKGROUND

• Awada A, Albanell J, Canney PA, Dirix LY, Gil T, Cardoso F, Gascon P, Piccart MJ, Baselga J. Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study. Br J Cancer. 2008 May 6;98(9):1500-7. doi: 10.1038/sj.bjc.6604347. Epub 2008 Apr 29.

  PMID: 18454159 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bortezomib; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yan-xia Shi, Doctor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanxia Shi, Doctor

CONTACT

86-020-87343486; shiyx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single-center, non-randomized, open-label, phase I study

Study Record Dates

• First Submitted: March 16, 2025
• First Posted: March 28, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)