Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

• Status: Unknown status
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hallym University Medical Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Aprepitant; BB 1101; Cisplatin; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Fosaprepitant; Ramosetron

Criteria

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