An Exploratory Study on Efficacy and Safety of Fosaprepitant and Palonosetron Hydrochloride for Injection in Preventing CINV From Multi-Agent HEC

An Exploratory Study on the Efficacy and Safety of Fosrolapitant and Palonosetron Hydrochloride for Injection in Preventing Nausea and Vomiting Caused by Highly Emetogenic Multi-Agent Chemotherapy

This prospective, multicenter, non-comparative, open-label trial design aims to evaluate the efficacy and safety of Fosrolapitant and Palonosetron Hydrochloride for Injection in preventing nausea and vomiting induced by hyperemetic chemotherapy (HEC) over multiple days. Eligible subjects were screened and assigned to Arm 1 or Arm 2 according to medical protocol. Arm 1: Fosrolapitant and Palonosetron Hydrochloride for Injection + Dexamethasone + Olanzapine; Arm 2: Fosrolapitant and Palonosetron Hydrochloride for Injection + Dexamethasone. Study drug administration commenced within 48 hours post-randomization, with follow-up visits and examinations completed as per protocol.

Inclusion Criteria:

• Aged 18-75 years, any gender, voluntarily signed informed consent form (ICF), with good compliance;

• Histologically or cytologically confirmed malignant solid tumour;

• No prior exposure to any chemotherapeutic agents;

• First-time participants with malignant solid tumours scheduled to receive a treatment regimen based on multi-day HEC chemotherapy (HEC refers to the risk of anti-tumour drug-induced nausea and vomiting as defined in the 2023 Edition of the Chinese Guidelines for the Prevention and Treatment of Nausea and Vomiting Associated with Anti-tumour Therapy; 'multi-day' denotes each chemotherapy cycle lasting at least 3 days);

• No impairment in speech, hearing, or comprehension;

• Expected survival ≥ 3 months;

• ECOG : 0-1;

• Organ function must be adequate and meet the following criteria:

  1. Neutrophil count ≥ 1.5 × 10⁹/L;
  2. Haemoglobin ≥ 90 g/L;
  3. Platelet count ≥ 100 × 10⁹/L;
  4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  5. In patients without known liver metastases, aspartate aminotransferase ≤ 2.5 × ULN and/or alanine aminotransferase ≤ 2.5 × ULN (for patients with liver metastases, may be relaxed to ≤ 5 × ULN);
  6. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 ml/min;
  7. Electrocardiogram: QTc ≤ 450 ms (males), QTc ≤ 470 ms (females);
  8. Echocardiogram: LVEF (left ventricular ejection fraction) ≥ 50%.

• Female subjects of childbearing potential, and male subjects with female partners of childbearing potential, must use one form of effective contraception from the time of signing the informed consent form until 6 months after the last dose (see Appendix). Female subjects of childbearing potential must have a negative blood pregnancy test within 72 hours prior to enrolment and must not be breastfeeding.

Exclusion Criteria:

• Subjects with symptomatic brain metastases or any symptoms suggestive of brain metastases or intracranial hypertension;
• Subjects who have received radiotherapy within 7 days prior to enrolment, extensive radiotherapy (e.g., whole-chest or whole-abdomen radiotherapy) within 3 months prior to enrolment, local palliative radiotherapy (e.g., for bone or lymph node metastases) within 1 month prior to enrolment, or who are scheduled to undergo any radiotherapy during the study period;
• Administration within 2 days prior to enrolment of medications with potential antiemetic effects: 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, or secloperazine;
• Initiation of benzodiazepine or opioid therapy within 2 days prior to enrolment (excluding zolpidem, temazepam, or midazolam administered alone daily);
• Subjects who commenced morphine use within 7 days prior to enrolment (excluding those on stable doses);
• Systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone, or prednisolone) or sedating antihistamines (e.g., diphenhydramine) administered within 7 days prior to enrolment (Note: Single-dose steroids for contrast allergy prophylaxis, or topical/inhaled administration are permitted);
• Use of palonosetron within 14 days prior to enrolment;
• Use of NK-1 receptor antagonists within 28 days prior to enrolment;
• Vomiting and/or retching, nausea occurring within 24 hours prior to enrolment;
• Presence of poorly controlled serosal effusions, including pleural effusion, ascites, pericardial effusion (exclusion may be waived if controlled by treatment and stable for ≥2 weeks);
• Severe cardiovascular disease within 3 months prior to enrolment, including but not limited to acute myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] Class II to IV), or history of severe cardiac conduction abnormalities (e.g., torsades de pointes ventricular tachycardia);
• Concurrent active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), active hepatitis C (HCV-Ab positive with HCV-RNA ≥ ULN), known acquired immunodeficiency syndrome (AIDS) or HIV-positive status, or syphilis-positive status;
• Concurrent conditions precluding dexamethasone administration, such as active infections (e.g., pneumonia) or uncontrolled conditions (e.g., diabetic ketoacidosis, intestinal obstruction);
• Known contraindications and/or allergies to study medications;
• Participation in another clinical trial within 30 days prior to enrolment (as determined by the use of study medication);
• Subjects deemed by the investigator to have other conditions rendering them unsuitable for this study.