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Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

Phase 2
Conditions
Solid Tumour
Postoperative Nausea and Vomiting
Interventions
Registration Number
NCT01046461
Lead Sponsor
Hallym University Medical Center
Brief Summary

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

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%.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
41
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ramosetron, Aprepitant, DexamethasoneRamosetron, Aprepitant, Dexamethasone-
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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 nauseauntil 1 month after chemotherapy
Time to first occurrence of vomitinguntil 1 month after chemotherapy
Adverse events reported using CTCAE v3.0until 1 month after chemotherapy

Trial Locations

Locations (1)

Hallym University Sacred Heart Hospital

🇰🇷

Anyang-si, Gyeonggi-do, Korea, Republic of

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