First-line Treatment of Advanced/unresectable DDLPS

Официальное название

Liposomal Doxorubicin Hydrochloride and Apatinib in Combination with Camrelizumab for the First-line Treatment of Advanced/unresectable Dedifferentiated Liposarcoma

Обзор

Evaluating the efficacy and safety of liposomal doxorubicin hydrochloride and apatinib in combination with camrelizumab for the first-line treatment of advanced/unresectable dedifferentiated liposarcoma

Подробное описание

Based on the clinical benefits provided by doxorubicin liposome, apatinib and camrelizumab treatment in STS, this study intends to explore the efficacy and safety of doxorubicin liposome hydrochloride and apatinib combined with camrelizumab in the first-line treatment of advanced/unresectable dedifferentiated liposarcoma with the aim of providing a better therapeutic option for the clinic.

Вмешательства

• Препарат Liposomal Doxorubicin (Doxil)
  30 mg/m2, d1, IV
• Препарат Apatinib
  250 mg, qd
• Препарат Camrelizumab
  200 mg, d1, IV

Первичные конечные точки

• overall response rate, ORR [Срок оценки: up to two years]

Вторичные конечные точки (3)

• progression free survival, PFS [Срок оценки: up to three years]
• overall survival, OS [Срок оценки: up to three years]
• adverse events, AE [Срок оценки: up to three years]

Критерии участия

Критерии включения

• Age 18-75 years, male or female;
• Histologically confirmed dedifferentiated liposarcoma;
• metastatic stage not having received systemic therapy;
• no brain metastases;
• ECOG PS: 0\~1 points;
• normal function of major organs, meeting the following requirements (within 7 days prior to initiation of study treatment): 1)Left ventricular ejection fraction (LVEF) ≥50%; 2)Normal electrocardiogram; 3)Hemoglobin \[HB\] ≥ 90 g/L; 4)Absolute neutrophil count \[ANC\] ≥1.5×109/L; 5) Platelet \[PLT\] ≥100×109/L; 6)Serum total bilirubin \[TBIL\] ≤1.5 times the upper limit of normal (ULN); 7) alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] <2.5 × ULN; if there are liver metastases, ALT and AST ≤5 × ULN; 8) Serum creatinine \[Cr\] ≤ 1 × ULN or endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
• women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and voluntarily use an appropriate method of contraception for the duration of the observation period and for 8 weeks after the final administration of study drug; in the case of males, they should be surgically sterilized or agree to use an appropriate method of contraception for the duration of the observation period and for 8 weeks after the final administration of study drug;
• expected to have good compliance and be able to follow up on efficacy and adverse effects as required by the protocol;
• sign an informed consent form.

Критерии исключения

• patients with recurrence within six months of postoperative adjuvant therapy;
• previous adjuvant or neoadjuvant phase with cumulative dose of doxorubicin, liposomal doxorubicin, or other anthracyclines ≥ 240 mg/m2;
• Use of PD-1 or PD-L1 inhibitors in prior adjuvant or neoadjuvant phase;
• patients with prior adjuvant or neoadjuvant phase use of apatinib mesylate and patients with prior treatment with vascular endothelial growth inhibitor-targeted agents such as sunitinib, sorafenib, bevacizumab, imatinib, famitinib, pazopanib, regorafenib, and erlotinib.
• Other active malignancies within 5 years or concurrently;
• central nervous system involvement;
• clinical symptoms or diseases of the heart that are not well controlled, such as (1) cardiac insufficiency of grade II or higher according to the New York Heart Association (NYHA) criteria or cardiac ultrasound: LVEF (Left Ventricular Ejection Fraction) < 50%; (2) unstable angina pectoris; (3) myocardial infarction within 1 year prior to the start of study treatment; (4) clinically significant supraventricular or ventricular arrhythmia Need for treatment or intervention: (5) QTc >450 ms (men); QTc >470 ms (women) (QTc intervals are calculated using the Fridericia formula; if the QTc is abnormal, three consecutive measurements may be taken at approximately 2-minute intervals and averaged);
• patients with signs or history of bleeding, regardless of severity; any bleeding or bleeding event CTCAE grade 3 within 4 weeks prior to enrollment, unhealed wounds, ulcers, or fractures
• those with hypertension that cannot be reduced to the normal range (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) with antihypertensive medication (based on the average of BP readings obtained from ≥2 measurements) are permitted to achieve the above parameters with the use of antihypertensive therapy;
• patients with severe hepatic or renal insufficiency (grade 4);
• poorly controlled diabetes mellitus (FBG) > 10 mmol/L);
• Patients with active ulcers, intestinal perforation, intestinal obstruction;
• Routine urinalysis showing urinary protein++, confirming 24-hour urine protein quantification >1.0g;
• Presence of active autoimmune disease or history of autoimmune disease with possible relapse;
• Uncontrolled infection or unexplained fever >38.5°C at screening;
• a known history of severe allergy to the study drug;
• other patients deemed unsuitable for inclusion by the treating physician.

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

Китай · 1 центр

• Fudan University, Cancer Hospital — Шанхай

Идентификаторы

NCT: NCT06694324 · Fudan-CMS-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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