Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial

Официальное название

Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial

Обзор

The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are: * Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP. * Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment. Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab. Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.

Вмешательства

• Препарат disitamab vedotin
  disitamab vedotin 2mg/kg iv q2w
• Препарат Pyrotinib
  pyrotinib 400mg po q28d
• Препарат trastuzumab
  trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d
• Препарат Pertuzumab
  pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d
• Препарат taxane drug
  Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations

Первичные конечные точки

• Progression Free Survival (PFS) [Срок оценки: Estimated 30 months]

Вторичные конечные точки (7)

• Overall Survival (OS) [Срок оценки: Estimated 8 years]
• Disease control rate (DCR) [Срок оценки: Estimated 30 months]
• Objective Response Rate (ORR) [Срок оценки: Estimated 30 months]
• Clinical Benefit rate (CBR) [Срок оценки: Estimated 30 months]
• Adverse Events (Based on CTCAE 5.0 standards) [Срок оценки: From informed consent through 28 days following treatment completion]
• Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) [Срок оценки: Estimated 30 months]
• Exploration of biomarkers [Срок оценки: Estimated 30 months]

Критерии участия

Критерии включения

• Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;
• Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);
• No previous chemotherapy regimen for metastatic breast cancer;
• At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);
• Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;
• Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);
• Patients with adequate organ function before enrollment:

• White Blood Cell (WBC) ≥ 3.0 x 10\^9/L;
• Neutrophil granulocyte (ANC) ≥1.5 x 10\^9/L;
• Platelet (PLT) ≥70×10\^9/L;
• Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):

• Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
• Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
• serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;
• . Normal cardiac function;

• Left ventricular ejection fraction (LVEF) ≥ 55%;
• QT-interval corrected with Fridericia (QTcF) ≤ 470ms;
• Hormone receptor status is clear;
• Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;
• Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.

Критерии исключения

• Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
• Patients with known hypersensitivity to the active ingredient or other components of the study drug;
• Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
• Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen Memorial Hospital,Sun Yat-sen University — Гуанчжоу

Публикации

• Koleva-Kolarova RG, Oktora MP, Robijn AL, Greuter MJW, Reyners AKL, Buskens E, de Bock GH. Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. 2017 Apr;55:16-25. doi: 10.1016/j.ctrv.2017.01.001. Epub 2017 Feb 20. PMID 28288388
• Mendes D, Alves C, Afonso N, Cardoso F, Passos-Coelho JL, Costa L, Andrade S, Batel-Marques F. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer--a systematic review. Breast Cancer Res. 2015 Nov 17;17:140. doi: 10.1186/s13058-015-0648-2. PMID 26578067
• Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36( PMID 29846122
• Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortes J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. PMID 32171426
• Glockner S, Buurman H, Kleeberger W, Lehmann U, Kreipe H. Marked intratumoral heterogeneity of c-myc and cyclinD1 but not of c-erbB2 amplification in breast cancer. Lab Invest. 2002 Oct;82(10):1419-26. doi: 10.1097/01.lab.0000032371.16521.40. PMID 12379776
• Shin SJ, Hyjek E, Early E, Knowles DM. Intratumoral heterogeneity of her-2/neu in invasive mammary carcinomas using fluorescence in-situ hybridization and tissue microarray. Int J Surg Pathol. 2006 Oct;14(4):279-84. doi: 10.1177/1066896906293055. PMID 17041191
• Brunelli M, Manfrin E, Martignoni G, Miller K, Remo A, Reghellin D, Bersani S, Gobbo S, Eccher A, Chilosi M, Bonetti F. Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/CAP criteria. Am J Clin Pathol. 2009 May;131(5):678-82. doi: 10.1309/AJCP09VUTZWZXBMJ. PMID 19369627
• Cortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa21 PMID 35320644

Идентификаторы

NCT: NCT06278870 · SYSKY-2023-431-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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