Clinical trial NCT01046461: Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Solid Tumour
Postoperative Nausea and Vomiting
Keywords: Ramosetron
aprepitant
dexamethasone
cancer
chemotherapy
antiemetics
cisplatin
nausea
vomiting
high dose cisplatin
Lead sponsor: Hallym University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-01-12
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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%.

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

Primary outcomes:
measure: 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)
timeFrame: from chemotherapy day 1 to day 5
Secondary outcomes:
measure: CR rate of RAD for the prevention of acute and delayed phase of CINV (from 0 to 24 hours /from 2 to 5 days)
timeFrame: until 1 month after chemotherapy
measure: Severity of nausea
timeFrame: until 1 month after chemotherapy
measure: Time to first occurrence of vomiting
timeFrame: until 1 month after chemotherapy
measure: Adverse events reported using CTCAE v3.0
timeFrame: until 1 month after chemotherapy
Other outcomes:
Locations:
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
Study officials:
affiliation: Hallym University Medical Center
name: Hyo Jung Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
References: