Aprepitant Triple Therapy for the Prevention of CINV in Nondrinking and Young Women Who Received Moderately Emetogenic Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to study whether adding Aprepitant to Palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI or FOLFOX chemotherapy regimen among gastrointestinal malignancy patients with high risk factors of chemotherapy-associated adverse events.

Detailed Description
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The purpose of this study is to study whether adding Aprepitant to Palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI or FOLFOX chemotherapy regimen after curative effect among gastrointestinal malignancy patients with high risk factors of chemotherapy-associated adverse events.This study will observe and evaluate the incidence and severity of nausea and vomiting as well as the effectiveness of corresponding treatment(with or without Aprepitant) during Day 1 to Day 5 from the beginning of chemotherapy.

Official Title
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Efficacy of Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Nondrinking Women Younger Than 50 Years Who Received Moderately Emetogenic Chemotherapy: A Randomized, Double-blind, Phase Ⅲ Trial

Conditions
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Gastrointestinal Neoplasms, Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Aprepitant
* Drug: Palonosetron
* Drug: Dexamethasone
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed by pathology as gastrointestinal carcinoma and no previous FOLFOX or FOLFIRI based regimen chemotherapy history. Female. Adult patients ( ≥ 18, ≤ 50 years of age) No long-term or excessive alcohol intake history:1.Alcohol intake less than 5 times per week; 2.Alcohol intake less than 100g per day. Performance status ECOG 0-1 Adequate haematological, hepatic, renal and metabolic function parameters: Leukocytes : 3,500-10,000/mm3, ANC ≥ 1,500/mm3, Platelets ≥ 90,000/mm3, Hb > 9g/dl (may be transfused or treated with erythropoietin to maintain or exceed this level), Serum creatinine ≤ 1 x upper limit of normal, Bilirubin ≤ 1.5 x upper limit of normal, Serum AST, ALT, ALP ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases. Negative pregnancy test. If pregnancy test were positive, subject should be included in the trial only when the subsequent pregnancy test is negative. Ability of reading, comprehending and finishing trial questionnaires and record, including VAS (Visual Analogue Scale) question. Before subject registration, written informed consent must be given according to local regulations. Exclusion Criteria: Pregnant women without morning sickness. Presence of gastrointestinal tract obstruction or electrolyte imbalance. Any history of central nervous system disease(e.g. Primary brain tumour, seizure not controlled with standard medical therapy, brain metastases or history of stroke). Contraindication of glucocorticoid:1.Infection of virus, bacteria or fungus uncontrolled by antibiotics; 2.Active stomach or duodenum ulcer; 3.Severe hypertension, atherosclerosis, diabetes; 4.Osteoporosis;5.Corneal ulcer; 6.Pregnancy; 7.Reparative phase of trauma, operation or fraction; 8.Hypercortisolism; 9.Severe mental disorder or epilepsy; 10.Inadequate cardiac or renal function. Mental disability or severe emotional or mental disorder. Active infection(e.g. pneumonia, hepatitis) or any uncontrolled disease(e.g.diabetic ketoacidosis) that may affect study outcome or expose patients to unnecessary risk. Usage of any illicit drug, including medical marijuana or alcohol abusing(China drug dependence criteria). Treatment of unapproved medicine in the previous 4 weeks. Concomitant therapy of psychotropic medicine such as olanzapine. Hypersensitivity history towards Aprepitant, 5-HT3 receptor antagonist or dexamethasone. Previous treatment of Aprepitant. Unable to swallow capsules. Main researchers considered that the patient is unsuited to the trial. Unable or unwilling to follow research programme.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palonosetron/Dexamethasone/Aprepitant<br> | Drug: Aprepitant<br>* Aprepitant is manufactured by Merck & Co. for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It was approved by the FDA in 2003<br>Drug: Palonosetron<br>* Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is used for the control of delayed CINV-nausea and vomiting and there are tentative data to suggest that it may be more effective than granisetron.<br>Drug: Dexamethasone<br>* Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis.<br>|
| Placebo Comparator: Palonosetron/Dexamethasone/Placebo<br> | Drug: Palonosetron<br>* Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is used for the control of delayed CINV-nausea and vomiting and there are tentative data to suggest that it may be more effective than granisetron.<br>Drug: Dexamethasone<br>* Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis.<br>Drug: Placebo Oral Tablet<br>* In the current clinical trial, placebo oral tablet is provided as a substance for Aprepitant with no active therapeutic effect.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate during the overall phase | The proportion of patients without emesis episodes or rescue medication use during the overall phase (0-120 h) | Up to 1-2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate in the acute phase | The proportion of patients without emesis episodes or rescue medication use during the acute phase (0-24h) | Up to 1-2 months | 
| Complete response rate in the delayed phase | The proportion of patients without emesis episodes or rescue medication use during the delayed phase (25-120 h) | Up to 1-2 months | 
| No vomiting rate in the acute phase, delayed phase and overall phase | The proportion of no vomiting (no vomiting or retching episodes) in the acute phase, delayed phase and overall phase | Up to 1-2 months | 
| Affection caused by CINV reported by patients |  | Up to 1-2 months | 
| Effects of CINV on daily life |  | Up to 1-2 months |