A Clinical Study on Prophylactic RespOnse To hEtrombopag for Secondary Prevention in Anti-Cancer Therapy-induced Thrombocytopeniae

Обзор

This study is a prospective clinical study enrolling breast cancer patients at high risk of chemotherapy-induced thrombocytopenia (CTIT). It aims to investigate the efficacy and safety of hetrombopag in the secondary prophylaxis of CTIT. Breast cancer patients with histologically or cytologically confirmed disease were enrolled after signing the informed consent form and were randomly assigned in a 1:1:1 ratio to three Arms. Stratification factors for randomization included the number of prior antineoplastic treatment cycles (\>2 cycles vs. ≤2 cycles). Arm 1: No prophylactic use of hetrombopag Arm 2: Hetrombopag at an initial dose of 7.5 mg once daily, administered from Day 1 of the first chemotherapy cycle (C1D1) continuously until the end of the second chemotherapy cycle Arm 3: Hetrombopag at an initial dose of 7.5 mg once daily, administered from Day 1 (C1D1) to Day 14 (C1D14) of the first chemotherapy cycle; the dosage and administration schedule in the second chemotherapy cycle were identical to those in the first cycle; Treatment continued until patients completed the protocol-specified treatment and follow-up, experienced intolerable toxicity, withdrew informed consent, initiated alternative antitumor therapy, died, or met any other treatment discontinuation criteria specified in the protocol, whichever occurred first.

Вмешательства

• Препарат Continuous Hetrombopag for 2 Cycles
  Hetrombopag at an initial dose of 7.5 mg once daily, administered from Day 1 of the first chemotherapy cycle (C1D1) continuously until the end of the second chemotherapy cycle
• Препарат Cyclic 14-day Hetrombopag for 2 Cycles
  Hetrombopag at an initial dose of 7.5 mg once daily, administered from Day 1 (C1D1) to Day 14 (C1D14) of the first chemotherapy cycle

Первичные конечные точки

• Incidence of grade ≥2 thrombocytopenia (PLT < 75×10⁹/L) [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]

Вторичные конечные точки (6)

• Duration of grade ≥2 thrombocytopenia (PLT < 75×10⁹/L) [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]
• Incidence and duration of grade ≥3 thrombocytopenia (PLT < 50×10⁹/L) [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]
• Proportion of patients who successfully completed two chemotherapy cycles without thrombocytopenia-related modifications to subsequent antineoplastic therapy [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]
• Proportion of patients without rescue therapy for thrombocytopenia (e.g., platelet transfusion, interleukin-11, recombinant human thrombopoietin) [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]
• Nadir and peak platelet counts [Срок оценки: At the end of Cycle 2 (each cycle ≥21 days)]
• Incidence of adverse events [Срок оценки: From enrollment to 21 days after the last dose of study drug]

Критерии участия

Критерии включения

• Age ≥ 18 years;
• Patients with histopathologically confirmed breast cancer;
• Receiving or expected to receive chemotherapy-based antitumor therapy with a cycle length of ≥21 days, and anticipated to receive ≥2 cycles of therapy;
• ECOG performance status 0-2;
• Platelet count meeting \*\*one\*\* of the following criteria:

• Nadir platelet count < 50×10⁹/L in the previous antitumor treatment cycle;
• Nadir platelet count ≥ 50×10⁹/L but < 75×10⁹/L in the previous antitumor treatment cycle, accompanied by \*\*high risk factors for bleeding\*\*\*;
• Platelet count ≥ 100×10⁹/L at enrollment;
• Patients with breast cancer plus other malignancies are allowed, provided that the treatment plan is primarily for breast cancer;
• Adequate organ function:

• Bone marrow: ANC ≥ 1.5×10⁹/L; hemoglobin ≥ 8 g/dL;

• Hepatic and renal function: total bilirubin ≤ 1.5 × ULN; ALT, AST ≤ 2.5 × ULN (or ≤ 5 × ULN in the presence of liver metastasis); serum creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault formula);

• Coagulation: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN;
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose, not be breastfeeding, and agree to use effective contraception during the study and for 7 days after the last dose of study drug.

Male subjects with female partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 7 days after the last dose of study drug; sperm donation is prohibited during the study;

• Life expectancy ≥ 3 months;
• Voluntarily participate in the study, sign the informed consent form, have good compliance, and be willing to comply with follow-up procedures.

• High risk factors for bleeding History of bleeding; prior treatment with platinum agents, gemcitabine, cytarabine, anthracyclines, PARP inhibitors (e.g., niraparib), etc.; combination of targeted agents and chemotherapeutic agents known to increase the risk of thrombocytopenia; history of radiotherapy or ongoing radiotherapy, especially to long bones and flat bones (e.g., pelvis, sternum).

Критерии исключения

• Presence of hematological disorders, including but not limited to leukemia, primary immune thrombocytopenia, myeloproliferative neoplasms, multiple myeloma, and myelodysplastic syndromes;
• Uncontrolled active infection;
• History of arterial or venous thrombosis;
• Patients with bleeding tendency, or evidence of inherited bleeding diathesis or coagulation disorders;
• Pregnant or breastfeeding women, or female patients of childbearing potential not using effective contraception;
• Participation in another clinical trial of thrombopoietic agents within 4 weeks prior to enrollment;
• Presence of uncontrolled neurological or psychiatric disorders, poor compliance, or inability to cooperate and report treatment-related reactions;
• Bone marrow involvement;
• Administration of rhTPO or rhIL-11 within 7 days prior to enrollment;
• Hypersensitivity to the study drug(s).

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

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Qin S, Wang Y, Yao J, Liu Y, Yi T, Pan Y, Chen Z, Zhang X, Lu J, Yu J, Zhang Y, Cheng P, Mao Y, Zhang J, Fang M, Zhang Y, Lv J, Li R, Dou N, Tang Q, Ma J. Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study. Ther Adv Med Oncol. 2024 Jun 14;16:17588359241260985. do PMID 38882443
• Kuter DJ. Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies. Haematologica. 2022 Jun 1;107(6):1243-1263. doi: 10.3324/haematol.2021.279512. PMID 35642485
• Jin G, Wu Y, She Z, Ma X, Deng S, Wang W, Wu Y, Li Q. Prophylactic Administration of Recombinant Human Thrombopoietin in the Secondary Prevention of Thrombocytopenia Induced by XELOX Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer. Am J Ther. 2021 Apr 7;28(4):e513-e516. doi: 10.1097/MJT.0000000000001331. No abstract available. PMID 33852489
• Li Q, Jin G, Jiang C, Zhang Z, Hou J, Zhao J, Chen F, Li Z. Prophylactic administration of recombinant human thrombopoietin attenuates XELOX or SOX regimen-induced thrombocytopaenia. Arch Med Sci. 2021 Aug 9;17(5):1440-1446. doi: 10.5114/aoms/141134. eCollection 2021. No abstract available. PMID 34522277
• Xu Y, Song X, Du F, Zhao Q, Liu L, Ma Z, Lu S. A Randomized Controlled Study of rhTPO and rhIL-11 for the Prophylactic Treatment of Chemotherapy-Induced Thrombocytopenia in Non-Small Cell Lung Cancer. J Cancer. 2018 Nov 25;9(24):4718-4725. doi: 10.7150/jca.26690. eCollection 2018. PMID 30588257
• Chen M, Li L, Xia Q, Chen X, Liao Z, Wang C, Shen B, Zhou M, Zhang Q, Zhang Y, Qian L, Yuan X, Wang Z, Xue C, An X, Liu B, Gu K, Hou M, Wang X, Wang W, Li E, Zhong J, Cheng J, Shu Y, Yang N, Wang H, Yang R, Liu T, Deng T, Ma F, Liao W, Qiu W, Chen Y, Chen X, Zhang M, Xu R, Li X, Feng J, Ba Y, Shi Y. A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thromb PMID 38515388
• Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol. 2000 Oct;95(10):2936-9. doi: 10.1111/j.1572-0241.2000.02325.x. PMID 11051371

Идентификаторы

NCT: NCT07647029 · 2603340-13

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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