Granisetron Transdermal Patch System for Prevention of CINV by CapeOX

Study Overview
=================
Brief Summary
-----------------
This study aims to explore the prevention of delayed chemotherapy induced by CAPOX regimen with granisetron transdermal patch。

Detailed Description
-----------------
Chemotherapy induced nausea and vomiting (CINV) is one of the most common side effects of tumor chemotherapy. Anorexia occurs in mild cases, electrolyte and acid-base balance disorders and malnutrition even occur in severe cases. Some patients will also have anxiety, fear and depression, which seriously affect the quality of life. This study explored the efficacy and safety of granisetron transdermal patch in the prevention of delayed nausea and vomiting caused by capeox chemotherapy.

Official Title
-----------------
Efficacy and Safety of Granisetron Transdermal Patch System for Prevention of Chemotherapy-induced Delayed Nausea and Vomiting by CapeOX：A Single-Arm, Open-Label, Phase II Study.

Conditions
-----------------
Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
-----------------
* Drug: Granisetron Transdermal Patch System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged >18 years. Eligible patients were diagnosed with a colorectal malignancy and scheduled to receive chemotherapy of CapeOx regimens. The Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores of patients were between 0 and 2. Patients with life expectancy≥6 months. Patients with the ability to understand the study and are willing to sign written informed consent document. Patients who were able to read, understand and follow the study procedures，and completed the questionnaire unaided. Exclusion Criteria: Patients with metabolic and haematological abnormalities who are unsuitable for chemotherapy. The following criteria are included: (1) Abnormal of blood routine: absolute neutrophil count(ANC) <1.5*109/L，white blood cell count (WBC)<3.0*109/L, platelet count (PLT) <100*109/L or hemoglobin (HB)<100g/L;(2) Abnormal liver function: aspartate aminotransaminase (AST) and/or aspartate aminotransferase (ALT)≥2.5*ULN, bilirubin is greater than 1.5 times the upper limit of normal value (ULN). In patients with known liver metastasis: AST is greater than or equal to 5 times the upper limit of normal value (ULN); ALT is greater than or equal to 5 times the upper normal value (ULN); (3) Abnormal renal function: serum creatinine is greater than 1.5*ULN. Patient had symptomatic primary or metastatic central nervous system malignancies. Patient used any drug with potential antiemetic effect within 7 days before receiving chemotherapy: 5-HT3 receptor antagonist (such as granisetron), phenothiazide (such as chlorpromazine), phenylbutanone (such as haloperidol), benzamide (such as metoclopramide), domperidone, cannabinoids, herbal medicine with potential antiemetic effect, anisodamine, seclizine, etc. Patients began to receive benzodiazepines or opioids within 48 hours before the first day of the study (except for single daily use of triazolam, temazepam or midazolam). Patients shall not receive any dose of systemic glucocorticoid treatment within 72 hours before the first day, except as specified in the protocol. Patients with historical or predisposing cardiac conduction abnormalities (such as torsade de pointe, ventricular tachycardia, long QT interval syndrome, or others), excluding incomplete right bundle branch block. Patients with severe cardiovascular diseases include acute myocardial infarction, unstable angina pectoris, significant membranous or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] class III-IV) and uncontrolled hypertension. Patients with severe emotional or mental disorders. Patients are taking or has used the following CYP3A4 inducers within 30 days before the first day of treatment, which will affect the efficacy of therapeutic drugs according to the evaluation of the researcher. Patients are taking or has used the following CYP3A4 substrates and inhibitors within 7 days before the first day of treatment, which will significantly increase the adverse events related to therapeutic drugs according to the evaluation of the investigator. Patients with active phase infection (e.g. pneumonia) or any uncontrolled disease (such as diabetic ketoacidosis or gastrointestinal obstruction), researchers believe that treatment may confuse research results or lead to uncertainty risk. Pregnant women, lactating women, or women of childbearing age with positive blood and/or urine HCG test results before the test. Male and female subjects did not take effective contraceptive measures, or planned to be pregnant within 6 months after the start of the trial. Patients have any medical history that the investigator believes may confound the results of the study or expose the patient to unnecessary risks.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Granisetron transdermal patch for the prevention and treatment of CINV
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Granisetron transdermal patch 3.1mg was given 48 hours before the first day of chemotherapy, Dexamethasone 12mg was taken orally on the first day of chemotherapy and dexamethasone 8mg was taken orally on the second and third days of chemotherapy,3.1mg granisetron transdermal patch was replaced on the 5th day of chemotherapy. Granisetron transdermal patch was removed and discarded on the 12th day of chemotherapy. | Drug: Granisetron Transdermal Patch System<br>* Granisetron transdermal patch 3.1mg was given 48 hours before the first day of chemotherapy, Dexamethasone 12mg was taken orally on the first day of chemotherapy and dexamethasone 8mg was taken orally on the second and third days of chemotherapy,3.1mg granisetron transdermal patch was replaced on the 5th day of chemotherapy. Granisetron transdermal patch was removed and discarded on the 12th day of chemotherapy.<br>* Other names: Sancuso®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete control rate of delayed nausea and vomiting | Complete control rate of delayed nausea and vomiting (CC, 24 hours to 20 days before the first day of chemotherapy) | 24 hours to 20 days before the first day of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dates of delayed complete control | Definition of DDCC (dates of delayed complete control): from 24 hours to the 20th day of chemotherapy, the patient has no vomiting, no rescue treatment, no nausea (VAS < 5mm) or mild nausea (VAS < 25mm, mild); | from 24 hours to the 20th day of chemotherapy | 
| Complete control rate of acute nausea and vomiting | From 0 hour to 24 hours after chemotherapy, the patients did not vomit or need rescue treatment, and there was no incidence of nausea (VAS < 5mm) or mild nausea (VAS < 25mm). | 24 hours to 20 days before the first day of chemotherapy | 
| Proportion of subjects receiving remedial treatment | The investigator evaluated the degree of nausea and vomiting reported by the patient and the observed clinical manifestations according to the study In the judgment of the patient, remedial treatment can be used only when necessary to treat nausea or vomiting, and remedial treatment shall not be used when the patient does not have such symptoms. | 24 hours to 20 days before the first day of chemotherapy | 
| Changes of FLIE score before and after treatment | FLIE includes 9 questions about nausea and 9 questions about vomiting. The answers to each item were marked according to the visual analog scale with a score of 7. The nausea score, vomiting score and total score were calculated by summing the answers of each category and the total answer. Considering the purpose of this scheme, no impact on daily life is defined as that the average item score is greater than 6 points (total score > 108) according to 7 subscales. | 24 hours to 20 days before the first day of chemotherapy | 
| Changes of hospital anxiety and Depression Scale (HAD) scores before and after treatment | HAD is mainly used for screening anxiety and depression of patients in general hospitals. There are 14 items in this scale, including 7 Depression was assessed in items (21 points in total), and anxiety was assessed in 7 items (21 points in total). The score of depression subscale is 0-7, indicating no symptoms; 8-10 points are suspicious of depressive symptoms, and 11-21 points must have depressive state. Anxiety subscale score 0-7 Asymptomatic; The anxiety symptoms are suspicious on 8-10 points, and there must be anxiety on 11-21 points. | 24 hours to 20 days before the first day of chemotherapy |