Short-term Sintilimab in Combination With Taxane and Carboplatin for Neoadjuvant Therapy in Triple-negative Breast Cancer

Официальное название

Short-term Sintilimab in Combination With Taxane and Carboplatin for Neoadjuvant Therapy in Triple-negative Breast Cancer, an Open-labeled, Single Arm Trial

Обзор

The goal of this clinical trial is to learn about the efficacy and safety of short-term sintilimab in combination with taxane and carboplatin for neoadjuvant therapy in female early-stage triple-negative breast caner patients aging from 18 to 70 years with unilateral and invasive primary lesions above 1cm. The main questions it aims to answer are: 1. Does short-term sintilimab in combination with taxane and carboplatin lead to acceptible pathological complete response (pCR) rates, objective response rates (ORR), event-free survival (EFS) and overall survival (OS)? 2. Does short-term sintilimab in combination with taxane and carboplatin lead to less adverse events than regular-term ICIs reported in literature? Participants will be given 2 cycles of sintilimab, in combination with 4 cycles of taxane and carboplatin before surgery. An optional core-needle biopsy is performed after completing 2 cycles of sintilimab. All participants will be given regular follow-up post surgery according to ASCO guidelines.

Вмешательства

• Препарат Taxane and Carboplatin
  Nab-paclitaxel 100mg/m2+ Carboplatin AUC2 by intravenous (IV) infusion on day1, day8 and day15, every 4 weeks, for 4 cycles. or Docetaxel 75mg/m2+ Carboplatin AUC5 by intravenous (IV) infusion on day1, every 3 weeks, for 4 cycles. or Paclitaxel 80mg/m2+ Carboplatin AUC2 by intravenous (IV) infusion on day1, day8 and day15, every 4 weeks, for 4 cycles.
• Препарат Short-term Sintilimab
  Sintilimab 200mg by intravenous (IV) infusion on day1, every 3 weeks, for 2 cycles.
• Процедура Surgery
  All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Первичные конечные точки

• Pathologic Complete Response (pCR) Rates [Срок оценки: At surgery.]

Вторичные конечные точки (3)

• Objective Response Rates (ORR) [Срок оценки: At surgery.]
• Event-free survival (EFS) [Срок оценки: From Baseline to EFS event or date last known to be alive and event-free (up to 10 years)]
• Overall survival (OS) [Срок оценки: Time Frame: From Baseline to OS event or date last known to be alive (up to 10 years)]

Критерии участия

Критерии включения

• Age: 18-70 years, female;
• Unilateral, invasive, primary breast cancer, T≥1cm, cN0-3, M0;
• Immunohistochemistry(IHC): ER, PR<10%; HER-2 IHC "0", OR IHC "+", OR IHC "++" AND fluorescence in situ hybridization (FISH) negative;
• At least one measurable lesion according to RECIST V1.1;
• Newly or recently-collected core needle biopsy specimen of the primary lesion available for PD-L1 status determination;
• ECOG score 0 or 1 within 10 days prior to drug administration;
• Currently not pregnant or breastfeeding, and meet at least one of the following conditions:

• NOT women of childbearing potential (WOCBPs).
• WOCBPs that strictly adopt contraceptive measures during treatment and within at least 6 months after last drug administration.
• Organs well-functioned according to laboratory examination and imaging;
• Having good compliance with treatment plans, being capable of understanding the research process, and having signed a written informed consent.

Критерии исключения

• Bilateral invasive breast cancer or metastatic (Stage IV) breast cancer;
• With severe cardiovascular conditions:

• Myocardial infarction, acute coronary syndrome or PCI/CABG within 6 months;
• Current NYHA II-IV congestive heart failure (CHF) or past history of NYHA III-IV CHF.
• Immunodeficiency, or undergoing systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to drug administration;
• Active autoimmune diseases requiring systemic treatment within the past 2 years;
• Known history of active tuberculosis caused by Bacillus Tuberculosis;
• History of non infectious pneumonia requiring steroid treatment, or active pneumonia of all types;
• Severe systemic infections, or other serious illnesses;
• History of other malignant tumors within the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
• Known history of human immunodeficiency virus (HIV) infection;
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
• Known allergy or intolerance to therapeutic drugs or their excipients;
• History of receiving cytotoxic chemotherapy, endocrine therapy, biological therapy or radiation therapy for any reason;
• History of receiving anti PD-1, anti PD-L1, or anti PD-L2 drugs; or targeted drugs that act on stimulating or co-inhibitory T cell receptors (CTLA-4, OX 40, CD137 etc.);
• Enrolled in a study of an investigational drug/instrument and given intervention within 4 weeks prior to drug administration for regular drugs/instruments and within 12 months for anticancer or anti-proliferative drugs/instruments;
• Live vaccine (including but not limited to the following: measles, mumps, rubella, chickenpox/shingles, yellow fever, rabies, BCG, typhoid vaccines, and nasal influenza vaccines such as FluMist®) inoculation within 30 days prior to drug administration;
• History of mental illness or drug abuse that may affect compliance with trial requirements;
• During pregnancy or breastfeeding, or WOCABs that refuse to adopt strict contraceptive measures;
• Deemed to be not appropriate for participating in this study by researchers.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Abramson VG, Lehmann BD, Ballinger TJ, Pietenpol JA. Subtyping of triple-negative breast cancer: implications for therapy. Cancer. 2015 Jan 1;121(1):8-16. doi: 10.1002/cncr.28914. Epub 2014 Jul 16. PMID 25043972
• Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007 Mar;8(3):235-44. doi: 10.1016/S1470-2045(07)70074-8. PMID 17329194
• Scott LC, Mobley LR, Kuo TM, Il'yasova D. Update on triple-negative breast cancer disparities for the United States: A population-based study from the United States Cancer Statistics database, 2010 through 2014. Cancer. 2019 Oct 1;125(19):3412-3417. doi: 10.1002/cncr.32207. Epub 2019 Jul 8. PMID 31282032
• Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016 Nov;13(11):674-690. doi: 10.1038/nrclinonc.2016.66. Epub 2016 May 17. PMID 27184417
• Schott AF, Hayes DF. Defining the benefits of neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2012 May 20;30(15):1747-9. doi: 10.1200/JCO.2011.41.3161. Epub 2012 Apr 16. No abstract available. PMID 22508810
• Biswas T, Efird JT, Prasad S, Jindal C, Walker PR. The survival benefit of neoadjuvant chemotherapy and pCR among patients with advanced stage triple negative breast cancer. Oncotarget. 2017 Nov 20;8(68):112712-112719. doi: 10.18632/oncotarget.22521. eCollection 2017 Dec 22. PMID 29348858
• Chen VE, Gillespie EF, Zakeri K, Murphy JD, Yashar CM, Lu S, Einck JP. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer. Adv Radiat Oncol. 2017 Feb 7;2(2):105-109. doi: 10.1016/j.adro.2017.01.012. eCollection 2017 Apr-Jun. PMID 28740920

Идентификаторы

NCT: NCT05843292 · NeoSTEP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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