Bortezomib Plus Cisplatin in Recurrent or Metastatic Breast Cancer

Official title

Phase I Study to Evaluate the Safety and Preliminary Efficacy of Bortezomib Combined With Cisplatin in Patients With Recurrent or Metastatic Breast Cancer

Overview

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.

Interventions

• Drug Bortezomib (B)
  1.3mg/m2, IV, D1, D4, D8 and D11, every 3 weeks
• Drug Cisplatin (CDDP)
  50mg/m2, IV, D1-3, every 3 weeks
• Drug Bortezomib (B)
  1.5mg/m2, IV, D1, D4, D8 and D11, every 3 weeks
• Drug Bortezomib (B)
  1.7mg/m2, IV, D1, D4, D8 and D11, every 3 weeks
• Drug Cisplatin (CDDP)
  70mg/m2, IV, D1-3, every 3 weeks

Primary outcome measures

• Dose-limiting toxicities (DLTs) [Time frame: Within 28 days after the first dose.]
• Maximum Tolerated Dose (MTD) [Time frame: Within 28 days after the first dose.]

Secondary outcome measures (7)

• Progression- free survival ( PFS ) [Time frame: Within approximately 48 months.]
• Objective Response Rate (ORR) [Time frame: Within approximately 48 months]
• Disease Control Rate (DCR) [Time frame: Within approximately 48 months]
• Area Under the Curve (AUC) [Time frame: 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) [Time frame: 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.]
• Time to Maximum Plasma Concentration (Tmax) [Time frame: 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.]
• Half-Life (T1/2) [Time frame: 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.]

Eligibility criteria

Inclusion criteria

• 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:

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:

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Sun Yat-Sen University Cancer Center — Guangzhou

Publications

• 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.202 PMID 33304752
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT06900647 · 2024-FXY-300

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗