Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

Postoperative Nausea and Vomiting Clinical Trial

— RAD  

Official title:

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01046461
• Other study ID #: RAD1.0
• Status: Unknown status
• Phase: Phase 2
• First received: January 8, 2010
• Last updated: February 16, 2012
• Start date: January 2010
• Est. completion date: June 2012

Study information

• Verified date: February 2012
• Source: Hallym University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Unknown status
• Enrollment: 41
• Est. completion date: June 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Nausea
• Postoperative Nausea and Vomiting
• Solid Tumour
• Vomiting

Intervention

Drug:
• Ramosetron, Aprepitant, Dexamethasone
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

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-si	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
Hallym University Medical Center	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Severity of nausea		until 1 month after chemotherapy
Secondary	Time to first occurrence of vomiting		until 1 month after chemotherapy
Secondary	Adverse events reported using CTCAE v3.0		until 1 month after chemotherapy