Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer (RAD)
Primary Purpose
Solid Tumour, Postoperative Nausea and Vomiting
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Ramosetron, Aprepitant, Dexamethasone
Sponsored by
About this trial
This is an interventional prevention trial for Solid Tumour focused on measuring Ramosetron, aprepitant, dexamethasone, cancer, chemotherapy, antiemetics, cisplatin, nausea, vomiting, high dose cisplatin
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
Sites / Locations
- Hallym University Sacred Heart Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ramosetron, Aprepitant, Dexamethasone
Arm Description
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
CR rate of RAD for the prevention of acute and delayed phase of CINV (from 0 to 24 hours /from 2 to 5 days)
Severity of nausea
Time to first occurrence of vomiting
Adverse events reported using CTCAE v3.0
Full Information
NCT ID
NCT01046461
First Posted
January 8, 2010
Last Updated
February 16, 2012
Sponsor
Hallym University Medical Center
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01046461
Brief Title
Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Unknown status
Study Start Date
January 2010 (undefined)
Primary Completion Date
March 2012 (Anticipated)
Study Completion Date
June 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hallym University Medical Center
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumour, Postoperative Nausea and Vomiting
Keywords
Ramosetron, aprepitant, dexamethasone, cancer, chemotherapy, antiemetics, cisplatin, nausea, vomiting, high dose cisplatin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ramosetron, Aprepitant, Dexamethasone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Ramosetron, Aprepitant, Dexamethasone
Other Intervention Name(s)
Nasea, Emend
Intervention Description
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
Primary Outcome Measure Information:
Title
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)
Time Frame
from chemotherapy day 1 to day 5
Secondary Outcome Measure Information:
Title
CR rate of RAD for the prevention of acute and delayed phase of CINV (from 0 to 24 hours /from 2 to 5 days)
Time Frame
until 1 month after chemotherapy
Title
Severity of nausea
Time Frame
until 1 month after chemotherapy
Title
Time to first occurrence of vomiting
Time Frame
until 1 month after chemotherapy
Title
Adverse events reported using CTCAE v3.0
Time Frame
until 1 month after chemotherapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hyo Jung Kim, M.D.
Organizational Affiliation
Hallym University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hallym University Sacred Heart Hospital
City
Anyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
431-070
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer
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