Chemotherapy-induced Nausea and Vomiting
Conditions
Brief summary
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.
Interventions
On the first day of chemotherapy, a 60-minute intravenous infusion is administered prior to treatment
DRUGDexamethasone
On the first day of chemotherapy, take 12mg orally. From the second day of chemotherapy until 3 days after chemotherapy concludes, take 3.75mg orally twice daily
DRUGOlanzapine
From the first day of chemotherapy until three days after its completion, take 5mg orally each night before bedtime
Sponsors
Shanghai 6th People's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients achieving Complete Control of CINV from the first administration until 24 hours after the last administration of chemotherapy | from the first administration until 24 hours after the last administration of chemotherapy | To compare the proportion of subjects achieving and maintaining a complete response (defined as no emetic episode and no need for rescue medication) from the first administration until 24 hours after the last administration of chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients achieving Complete Control of CINV during the acute phase, delayed phase, and super-delayed phase | acute phase: from first chemotherapy administration until last administration; delayed phase: until 120 hours after last administration; super-delayed phase: from 120 hours to 168 hours after last administration | To compare the proportion of subjects achieving and maintaining a complete response (defined as no emetic episode and no need for rescue medication) during the specified period. |
| No significant nausea | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects with no significant nausea (defined as maximum nausea on a visual analogue scale \<25 mm) during the specified period. |
| No nausea | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects with no nausea (defined as maximum nausea on a visual analogue scale \<5 mm) during the specified period. |
| No emetic | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects with no emetic event during the specified period |
| No rescue medication | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects who received no rescue medication during the specified period. |
| Complete protection | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects with complete protection (defined as patients who experienced no emetic event and received no rescue medication and had no significant nausea) during the specified period). |
| Total control | from first chemotherapy administration until last administration, until 24 hours after last administration, until 120 hours after last administration, and from 120 hours to 168 hours after last administration | To compare the proportion of subjects with total control (defined as patients who experienced no emetic events and received no rescue medication and had no nausea) during the specified period. |
| The score using the functional living index-emesis (FLIE) questionnaire | from first chemotherapy administration to 168 hours after last administration | To compare the change of score using FLIE questionnaire before and after treatment. |
Countries
China
Outcome results
None listed