Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

NCT ID: NCT01046461

Last Updated: 2012-02-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-06-30

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%.

Conditions

Solid Tumour; Postoperative Nausea and Vomiting

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Ramosetron, Aprepitant, Dexamethasone

Group Type: EXPERIMENTAL

Ramosetron, Aprepitant, Dexamethasone

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Nasea; Emend

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Hallym University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hyo Jung Kim, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hallym University Medical Center

Locations

Hallym University Sacred Heart Hospital

Anyang-si, Gyeonggi-do, South Korea

Countries

South Korea

Other Identifiers

RAD1.0

Identifier Type: -

Identifier Source: org_study_id