An Exploratory Study of Fosrolapitant and Palonosetron Hyerocthoride for the Prevention of Nausea and Vomiting Induced by Highly Emetogenic ADC Therapy in Patients With Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Proportion of subjects achieving complete response (CR) during Days 0-21 after study drug administration in Cycle 1 (defined as no emetic episodes and no rescue medication use).
研究概览
简要总结
This study aims to evaluate the efficacy and safety of Fosrolapitant and Palonosetron Hydrochloride for Injection in preventing nausea and vomiting induced by highly emetogenic antibody-drug conjugate (ADC) therapy in patients with solid tumors. A total of 60 patients are planned to be enrolled and divided into two groups: Group A will receive Fosrolapitant and Palonosetron Hydrochloride for Injection plus Dexamethasone plus Olanzapine, and Group B will receive Fosrolapitant and Palonosetron Hydrochloride for Injection plus Dexamethasone.
详细描述
Antibody-drug conjugates (ADCs) have brought hope to cancer patients. For ADCs, nausea and vomiting are common adverse reactions. Compared with traditional chemotherapy, ADC-induced nausea and vomiting are usually more complex, with a higher risk of delayed nausea and vomiting. For example, trastuzumab deruxtecan, a HER2-targeted ADC, has a median time to onset of vomiting of 9.5 days and a median duration of 3 days, and a median time to onset of nausea of 3 days and a median duration of up to 10 days. Sacituzumab govitecan, a Trop-2-targeted ADC, has a median time to onset of vomiting of 24.5 days and a median duration of 1.5 days, and a median time to onset of nausea of 8 days and a median duration of 5.5 days. Fosrolapitant and Palonosetron Hydrochloride for Injection, an innovative fixed-dose combination antiemetic, was approved for marketing by the Center for Drug Evaluation (CDE) on May 27, 2025. The half-life of fosrolapitant in Fosrolapitant and Palonosetron Hydrochloride for Injection is as long as 188 h, which can cover the acute, delayed, and ultra-delayed phases (120-168 h) of anti-tumor treatment-induced nausea and vomiting. This study intends to use Fosrolapitant and Palonosetron Hydrochloride for Injection as the basis combined with dexamethasone ± olanzapine to explore its efficacy and safety in preventing nausea and vomiting caused by highly emetogenic ADCs, and also to observe the preventive effect of other standard treatment (fosaprepitant + palonosetron + dexamethasone) on nausea and vomiting caused by highly emetogenic ADCs. It also aims to identify signals for the optimal management model of highly emetogenic ADC-related nausea and vomiting, so as to better guide clinical practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years, either sex;
- •Pathologically confirmed malignant solid tumors;
- •Planned to receive initial highly emetogenic ADC therapy on a 3-week regimen;
- •Expected survival ≥3 months;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •Adequate organ function, meeting the following criteria:
- •Neutrophil count ≥1.5 × 10⁹/L;
- •Hemoglobin ≥90 g/L;
- •Platelet count ≥100 × 10⁹/L;
- •Total bilirubin ≤1.5 × ULN;
- •In patients without known liver metastases, aspartate aminotransferase ≤2.5 × ULN and/or alanine aminotransferase ≤2.5 × ULN (for patients with liver metastases, this may be relaxed to ≤5 × ULN);
- •Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min;
- •ECG: QTc ≤450 ms (male), QTc ≤470 ms (female);
- •Echocardiography: left ventricular ejection fraction (LVEF) ≥50%;
- •Female subjects of childbearing potential, and male subjects whose partners are women of childbearing potential, must use a highly effective method of contraception from the signing of the informed consent form until 35 days after the last dose; sperm donation is not permitted during the study. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 h before randomization and must be non-lactating. Subjects must clearly understand and voluntarily participate in this study and personally sign the informed consent form.
排除标准
- •Received, within 7 days before randomization, or planned to receive during the treatment period, abdominal radiotherapy (including at or below the diaphragmatic plane), pelvic radiotherapy, whole-body radiotherapy, or whole-brain radiotherapy;
- •Planned to receive highly emetogenic chemotherapy from Day 2 after ADC administration until the next treatment;
- •Prior use of other ADC drugs;
- •Use of medications with potential antiemetic efficacy within 2 days before the start of study treatment: first-generation 5-HT3 receptor antagonists (e.g., ondansetron), phenothiazines (e.g., prochlorperazine), butyrophenones (e.g., haloperidol), benzamides (e.g., metoclopramide), domperidone, cannabinoids, traditional Chinese medicines with potential antiemetic effects, scopolamine, cyclizine, etc.;
- •Initiation of benzodiazepines or opioids within 2 days before the start of study treatment (except triazolam, temazepam, or midazolam administered alone daily);
- •Initiation of morphine within 7 days before the start of study treatment (except those receiving a stable dose);
- •Receipt of systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone, or prednisolone) or sedating antihistamines (e.g., diphenhydramine) within 7 days before the start of study treatment (Note: single-dose steroids for prevention of contrast allergy and topical or inhaled administration are permitted);
- •Use of palonosetron within 14 days before the start of study treatment;
- •Use of NK-1 receptor antagonists within 28 days before the start of study treatment;
- •Use of specific CYP3A4 substrates (terfenadine, cisapride, astemizole) or CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, ketoconazole or itraconazole, diltiazem, etc.) within 7 days before the start of study treatment, or use of strong CYP3A4 inducers (e.g., phenobarbital, rifampin, phenytoin, carbamazepine, etc.) or specific CYP2D6 substrates (thioridazine, pimozide) within 28 days before randomization;
- •Vomiting and/or retching, or nausea, within 24 h before the start of study treatment;
- •Symptomatic brain metastases or any symptoms suggestive of brain metastases or intracranial hypertension;
- •Inadequately controlled serous cavity effusion, including pleural effusion, ascites, and pericardial effusion (those controlled after treatment and stable for ≥2 weeks may be enrolled);
- •Severe cardiovascular disease within 3 months before the start of study treatment, including but not limited to acute myocardial infarction, unstable angina, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] class II-IV), or history of serious cardiac conduction abnormalities (e.g., torsades de pointes);
- •Poorly controlled hypertension before the start of study treatment (two consecutive resting systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);
- •Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL), active hepatitis C (HCV-Ab positive and HCV-RNA ≥ upper limit of normal), acquired immunodeficiency syndrome (AIDS) or HIV-positive, or syphilis-positive;
- •Concomitant disease that precludes dexamethasone administration, such as active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction, etc.);
- •Known contraindications to NK-1 receptor antagonists, 5-HT3 receptor antagonists, or dexamethasone;
- •Participation in another clinical trial within 30 days before the start of study treatment (based on use of study drug);
- •Other circumstances considered by the investigator to make participation in this study inappropriate.
研究组 & 干预措施
Group A：Fosrolapitant and Palonosetron + Dexamethasone + Olanzapine
干预措施: Fosrolapitant and Palonosetron; Dexamethasone; Olanzapine (Drug)
Group B：Fosrolapitant and Palonosetron + Dexamethasone
干预措施: Fosrolapitant and Palonosetron; Dexamethasone (Drug)
结局指标
主要结局
Proportion of subjects achieving complete response (CR) during Days 0-21 after study drug administration in Cycle 1 (defined as no emetic episodes and no rescue medication use).
时间窗: Day 0-21 after first treatment cycle 1 dosing
Proportion of subjects achieving complete response (CR) during Days 0-21 after study drug administration in Cycle 1 (defined as no emetic episodes and no rescue medication use). Analysis of the primary study endpoint will be based on the intent-to-treat (ITT) population. The proportion of subjects achieving complete response (CR) during Days 0-21 after initiation of ADC administration in the first treatment cycle will be calculated for both groups. Descriptive between-group analysis of CR rates will be performed using the Cochran-Mantel-Haenszel (CMH) test.
次要结局
- The proportions of subjects with CR, no significant nausea, no nausea, no vomiting, no rescue medication use, complete protection, and complete control during the period.(After initiation of antitumor treatment：Acute: 0-24 hour; Delayed: 24-120 hours; Overall: 0-120 hours; Ultra-delayed: 120-168 hours；0 - 168 hours, 120 hours - next treatment and for the 2nd and subsequent treatment cycles 0 - 21 days)
- Time to treatment failure(up to 4 cycles (each cycle is 21 days))
- The proportions of subjects with nausea and vomiting reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0(up to 4 cycles (each cycle is 21 days))
- The proportions of subjects with Functional Living Index-Emesis (FLIE) assessment.(up to 4 cycles (each cycle is 21 days))