Clinical Study of HR20013 for Injection in Patients With Malignant Solid Tumors

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of HR20013 for injection for prevention of chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy.

Official Title
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Compared With Fosaprepitant Dimeglumine for Injection and Palonosetron Hydrochloride Injection, to Evaluate the Efficacy and Safety of HR20013 for Injection for Prevention of Chemotherapy-induced Nausea and Vomiting After Highly Emetogenic Chemotherapy

Conditions
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Prevention of Nausea and Vomiting Caused by Highly Emetogenic Chemotherapy

Intervention / Treatment
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* Drug: HR20013 for injection；dexamethasone
* Drug: fosaprepitant dimeglumine for injection；palonosetron hydrochloride injection；dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older, of either gender Has a diagnosed malignant tumor has never been treated with chemotherapy and is to receive the first course of cisplatin-based chemotherapy Predicted life expectancy of ≥ 3 months Has a performance status (ECOG scale) of 0 to 1 Adequate bone marrow, kidney, and liver function Women of childbearing potential must have negative pregnancy test (serum test) results within 72 hours prior to enrollment Able and willing to provide a written informed consent Exclusion Criteria: Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -7 through Day 8 Scheduled to receive any other chemotherapeutic agent with an high emetogenicity level from Day 2 through Day 8 Has taken the following agents within the last 48 hours 5-HT3 antagonists, Phenothiazines, Benzamides, Domperidone, Cannabinoids, Benzodiazepines Subjects receiving palonosetron hydrochloride within 14 days before randomization Subjects who previously received NK-1 receptor antagonists within 28 days prior to randomization Subjects with a history of myocardial infarction or unstable angina pectoris Subjects with atrioventricular block or cardiac insufficiency Subjects with poor blood pressure control after medication Subjects with symptomatic brain metastases or any symptoms suggestive of brain metastasis or intracranial hypertension Subjects who have experienced emetic events (vomiting or dry vomiting) or nausea within 24 hours before randomization Participated in clinical trials of other drugs (received experimental drugs) The investigators determined that other conditions were inappropriate for participation in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: HR20013 for injection + dexamethasone compared with fosaprepitant dimeglumine for injection + palonosetron hydrochloride injection + dexamethasone
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>HR20013 for injection + simulant of fosaprepitant dimeglumine for injection + simulant of palonosetron hydrochloride injection + dexamethasone | Drug: HR20013 for injection；dexamethasone<br>* HR20013 for injection；Drug for preventing nausea and vomiting caused by chemotherapy dexamethasone: Drug for preventing nausea and vomiting caused by chemotherapy<br>|
| Active Comparator: Treatment group B<br>simulant of HR20013 for injection + fosaprepitant dimeglumine for injection + palonosetron hydrochloride injection + dexamethasone + simulant of dexamethasone | Drug: fosaprepitant dimeglumine for injection；palonosetron hydrochloride injection；dexamethasone<br>* fosaprepitant dimeglumine for injection: Drug for preventing nausea and vomiting caused by chemotherapy palonosetron hydrochloride injection: Drug for preventing nausea and vomiting caused by chemotherapy dexamethasone: Drug for preventing nausea and vomiting caused by chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response during the overall phase after the start of the first cisplatin administration | To compare the rate of subjects achieving and maintaining a complete response (defined as no emetic episode and no need for rescue medication) after the start of the first cisplatin administration. | 0-120 hours after the start of the first cisplatin administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response during the acute phase, the delayed phase, >120-168 hours, and 0-168 hours after the start of the first cisplatin 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. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), >120-168 hours, and 0-168 hours after the first cisplatin administration | 
| Complete response during the acute phase, the delayed phase, the overall phase, >120-168 hours, and 0-168 hours after the start of the second cisplatin 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. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours, and 0-168 hours after the start of the second cisplatin administration | 
| No significant nausea | 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. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| No nausea | To compare the proportion of subjects with no nausea (defined as maximum nausea on a visual analogue scale <5 mm) during the specified period. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| No emetic | To compare the proportion of subjects with no emetic event during the specified period. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| No rescue medication | To compare the proportion of subjects who received no rescue medication during the specified period. | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| Complete protection | 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). | the acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| Total control | 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 acute phase (0-24 hours), the delayed phase (>24-120 hours), the overall phase (0-120 hours), >120-168 hours and 0-168 hours after the start of each cisplatin administration | 
| Time to treatment failure | Time to the first occurrence of emetic event or the first rescue medication. | During 0-168 hours after the start of each cisplatin administration | 
| The score using the functional living index-emesis (FLIE) questionnaire | To compare the change of score using FLIE questionnaire before and after treatment. | During 0-168 hours after the start of each cisplatin administration | 
| Number of participants with injection site reaction and with treatment-related adverse events as assessed by CTCAE v5.0 | To compare the number of participants with injection site reaction and with treatment-related adverse events as assessed by CTCAE v5.0. | 0 to 504 hours after the start of each cisplatin administration | 
| plasma concentration of HR20013 | To analyse the plasma concentration of HR20013 at the specified time points. | Evaluation time points include 1-2 hours, 5-10 hours, and 3 days after the start of the first HR20013 administration, and day 1 of the second HR20013 administration |