Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer (RAD)

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

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

Study Overview

• Status: Unknown
• Conditions: Postoperative Nausea and Vomiting; Solid Tumour
• Intervention / Treatment: Drug: Ramosetron, Aprepitant, Dexamethasone

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%.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, Korea, Republic of, 431-070
      • Hallym University Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramosetron, Aprepitant, Dexamethasone	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; Other Names: Emend; Nasea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hallym University Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Hyo Jung Kim, M.D., Hallym University Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): March 1, 2012
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: January 8, 2010
• First Submitted That Met QC Criteria: January 11, 2010
• First Posted (Estimate): January 12, 2010

Study Record Updates

• Last Update Posted (Estimate): February 17, 2012
• Last Update Submitted That Met QC Criteria: February 16, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: cisplatin; chemotherapy; cancer; nausea; vomiting; dexamethasone; aprepitant; Ramosetron; antiemetics; high dose cisplatin
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Aprepitant; Ramosetron
• Other Study ID Numbers: RAD1.0