Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

Study Overview
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Brief Summary
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Cisplatin is one of the most emetogenic drugs used in clinical practice and it could result in poor compliance with chemotherapy. The 5-HT3 receptor antagonists prevent vomiting in acute phase emesis after chemotherapy in 73 - 92% of cisplatin-treated patients when coadministered with steroids, but they appear to lack efficacy in the delayed phase emesis. Ramosetron, a new 5-HT3 receptor antagonists, has been shown to have equivalent efficacy and tolerability and a longer duration of effect than granisetron in preventing acute vomiting in patients undergoing cisplatin-containing chemotherapy. Acute phase emesis was prevented in 84.8% of patients receiving ramosetron plus dexamethasone, but the CR rate of total phase emesis was less than 60%. Aprepitant is a selective, high-affinity NK1 receptor antagonist. Adding aprepitant to 5-HT3 receptor antagonists and steroid improve CR rate of not only chemotherapy induced acute emesis and but also delayed emesis by 11-14 and 20 percentage points, respectively. But until now, there was no information that which 5-HT3 receptor antagonists is the best partner for aprepitant. Therefore, we initiated a prospective, open-label, phase II study to assess the efficacy and tolerability of a combination of ramosetron, aprepitant and dexamethasone (RAD) in the prevention of cisplatin based CINV in chemotherapy-naïve patients with solid cancer

Detailed Description
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Cisplatin is one of the most emetogenic drugs used in clinical practice and it could result in poor compliance with chemotherapy. The 5-HT3 receptor antagonists prevent vomiting in acute phase emesis after chemotherapy in 73 - 92% of cisplatin-treated patients when coadministered with steroids, but they appear to lack efficacy in the delayed phase emesis. Ramosetron, a new 5-HT3 receptor antagonists, has been shown to have equivalent efficacy and tolerability and a longer duration of effect than granisetron in preventing acute vomiting in patients undergoing cisplatin-containing chemotherapy. Acute phase emesis was prevented in 84.8% of patients receiving ramosetron plus dexamethasone, but the CR rate of total phase emesis was less than 60%.

Official Title
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A Phase II Study to Evaluate the Efficacy and Tolerability of Ramosetron, Aprepitant and Dexamethasone (RAD) in Preventing Cisplatin-induced Nausea and Vomiting in Chemotherapy-naïve Patients With Solid Cancer

Conditions
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Solid Tumour, Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: Ramosetron, Aprepitant, Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 -75 years, both sex ECOG performance status 0-2 Histologically proven solid cancer, chemotherapy-naïve patient Planed to receive cisplatin (≥ 50mg/m2) based, single day chemotherapy, No nausea or vomiting within 72 hours prior to chemotherapy Serum Cr < 2.5 mg/dl, or calculated CCr ≥ 50 ml/min Serum total bilirubin < 2 mg/dl, AST/ALT < 3 times the upper normal limit , ALP < 5 times the upper normal limit Absolute neutrophil count ≥ 1,500/μL, platelet ≥ 100,000/μL Expected life duration ≥ 3 months Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital Exclusion Criteria: Patients with active infection, severe heart disease, uncontrollable hypertension or diabetes mellitus, active gastric or duodenal ulcers, or pregnancy or breast-feeding Patients who should take steroid, antiemetics, pimozide, terfenadine, astemizole, cisapride, rifampin, carbamazepine, phenytoin, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir or nelfinavir for the treatment of other diseases Patients taking any medicine, which could affect study results, within 1 week before chemotherapy (or taking anti-emetics within 48 hours before chemotherapy). Prior to beginning chemotherapy, single-agent benzodiazepines as hypnotic is allowed, but it can't be receiving during day 1-6 of 1st chemotherapy cycle. Patients with symptomatic brain metastasis Patients with GI obstruction or other diseases that could provoke nausea and vomiting Patients receiving RT on brain, abdomen or pelvis within 2 weeks before chemotherapy Patients who cannot understand informed consent or express his/her condition Patients who cannot swallow drugs Patients who have known allergy or severe side effect on study drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramosetron, Aprepitant, Dexamethasone<br> | Drug: Ramosetron, Aprepitant, Dexamethasone<br>* Day 1: Aprepitant 125 mg PO, 1 hour before chemotherapy Ramosetron 0.6 mg IV, 30 min before chemotherapy Dexamethasone 12 mg PO, 30 min before chemotherapy Day 2 - 3: Aprepitant 80 mg PO. in the morning Dexamethasone 8 mg PO. in the morning Day 4 Dexamethasone 8 mg PO. in the morning<br>* Other names: Emend;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate of RAD for the prevention of chemotherapy induced nausea vomiting (CINV) during overall phase (form 1 to 5 days) (overall phase is defined as acute and delayed phase) |  | from chemotherapy day 1 to day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate of RAD for the prevention of acute and delayed phase of CINV (from 0 to 24 hours /from 2 to 5 days) |  | until 1 month after chemotherapy | 
| Severity of nausea |  | until 1 month after chemotherapy | 
| Time to first occurrence of vomiting |  | until 1 month after chemotherapy | 
| Adverse events reported using CTCAE v3.0 |  | until 1 month after chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ramosetron, aprepitant, dexamethasone, cancer, chemotherapy, antiemetics, cisplatin, nausea, vomiting, high dose cisplatin