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CTRI Number  CTRI/2018/09/015742 [Registered on: 18/09/2018] Trial Registered Prospectively
Last Modified On: 13/09/2018
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Comparing antiemetic regimens as maintenance therapy in highly emetogenic chemotherapy. 
Scientific Title of Study   A randomized open label trial comparing three antiemetic regimens (dexamethasone 8 mg/olanzapine 5 mg /olanzapine 10 mg) as maintenance therapy in patients who are on highly emetogenic chemotherapy. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Navdeep Singh 
Designation  DNB Medical Oncology Resident  
Affiliation  Dr B L Kapur Memorial hospital 
Address  Department of medical oncology OPD 7 BLK Super Speciality Hospital Pusa Road, New Delhi -110005

New Delhi
DELHI
110005
India 
Phone  9815879111  
Fax    
Email  navdeepsinghkailey116@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Amit Agarwal 
Designation  Head Of Department 
Affiliation  Dr B L Kapur Memorial hospital 
Address  Department of medical oncology OPD 7 BLK Super Speciality Hospital Pusa Road, New Delhi -110005

New Delhi
DELHI
110005
India 
Phone  9971611311  
Fax    
Email  amit.agarwal@blkhospital.com  
 
Details of Contact Person
Public Query
 
Name  Dr Navdeep Singh 
Designation  DNB Medical Oncology Resident  
Affiliation  Dr B L Kapur Memorial hospital 
Address  Department of medical oncology OPD 7 BLK Super Speciality Hospital Pusa Road, New Delhi -110005

New Delhi
DELHI
110005
India 
Phone  9815879111  
Fax    
Email  navdeepsinghkailey116@gmail.com  
 
Source of Monetary or Material Support  
BLK Super Speciality Hospital Department of medical oncology Pusa Road, New Delhi -110005,  
 
Primary Sponsor  
Name  Dr B L Kapur hospital  
Address  Department of medical oncology BLK Super Speciality Hospital Pusa Road, New Delhi -110005 
Type of Sponsor  Private hospital/clinic 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Navdeep Singh  Dr B L Kapur Memorial Hospital   OPD-7 Department of medical oncology BLK Super Speciality Hospital Pusa Road, New Delhi -110005
New Delhi
DELHI 
9815879111

navdeepsinghkailey116@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Dr B L Kapur Memorial Hospital Ethics Committee and its composition   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C00-D49||Neoplasms,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Dexamthasone  8mg per oral once a day for 4 days  
Intervention  Olanzapine   10 mg per oral once a day for 4 days  
Comparator Agent  olanzapine  5 mg per oral once a day for 4 days  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  Adult >18 year of age.
Absence of nausea and vomiting 24 hours before.
Patients up to PS-2.
Adequate organ function creatinine <1.5, hemoglobin > 8.
Histologically or cytologically confirmed malignant disease.
Patients who will receive high emetogenic cancer chemotherapy (HEC). 
 
ExclusionCriteria 
Details  Age > 80 years.
Contraindication to steroid use.
Uncontrolled diabetes.
Pregnant or breast-feeding.
History of psychosis.
Sensitivity to olanzapine. 
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Yet to be decided  year 2021 
 
Secondary Outcome  
Outcome  TimePoints 
to be decided   year 2021 
 
Target Sample Size   Total Sample Size="240"
Sample Size from India="240" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   20/09/2018 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="11"
Days="30" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   yet to be published 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  
Chemotherapy induced nausea and vomiting is quite a known problem in patients undergoing treatment for various oncologic diseases. It significantly affects the quality of life of patient and has both psychological and physical implications. In 1983, Coates et al. documented that patients undergoing chemotherapy reported nausea and vomiting as the first and second most severe side effects. Patients who
were on highly emetogenic agents in this era postponed, or even refused, potentially curative treatments. [1]  

Since the 1990s, several new classes of novel classes of antiemetic’s have been developed, studied and commercialized and are being used as universal standard in chemotherapy regimens .Efficient mediation of these unpleasant and undesirable symptoms results in increased quality of life for the patient, better heath outcome ,more patient tolerance and reduction in number of hospital days stay. The incidences may be as high as 60–80% or more depending on the chemotherapeutic agent used. A study on the Japanese population receiving moderately emetogenic chemotherapy (MEC) has been reported to produce an
incidence of nausea in 48 % patients even with use of antiemetic prophylaxis [2].

Only few newer antiemetic’s has been approved in the last few years and very few are under clinical trial. NK1receptor antagonists (NK1RA) like aprepitant and fosaprepitant or the recent additions like netupitant , orrolapitant are some significant developments in the recent years. Dexamethasone has been long used as effective agent for management of chemotherapy induced vomiting. Vardy et al [3] studied adverse reactions related to
dexamethasone when used to prevent late onset emesis in moderately emetogenic chemotherapy (MEC), including anthracycline plus cyclophosphamide (AC), and reported such moderate-to severe adverse reactions to DEX as insomnia (45%), indigestion and epigastric discomfort (27%), and agitation (27%). It is currently unknown whether daily dexamethasone for five consecutive days of cisplatin provides more harm than benefit due to the potential adverse effects of longer duration dexamethasone.A recent study published showed Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK1-RA and Palonosetron in HEC [4].

Olanzapine is atypical antipsychotic approved by the Food and Drug Administration (FDA).It blocks multiple neurotransmitters: dopamine at D1, D2, D3, and D4receptors; serotonin at 5-HT type 2a, 5-HT type 2c (5-HT2c), 5-HT3, and 5-HT type 6 receptors;catecholamines at alpha1-adrenergic receptors;acetylcholine at muscarinic receptors; and histamine at H1 receptors in the central nervous system [5, 6]. Common side effects are mild short-term sedation, weight gain and an increased risk of diabetes mellitus when used more than 6 months. As olanzapine act at multiple receptors, particularly the D2, 5-HT2c, and 5-HT3 receptors, which may be involved in nausea and vomiting, suggest its role as agent with anti emetogenic property. A single-institution phase 3 trial showed that olanzapine, when combined with a single dose of dexamethasone and a single dose of palonosetron, an HT3-receptor blocker, was effective in controlling early and longer-term nausea and vomiting in patients receiving highly emetogenic chemotherapy [7]. Additional single-institution phase 3 studies have shown that olanzapine when combined with standard  antiemetic agents improves control of nausea and vomiting in patients receiving moderately or highly emetogenic chemotherapy [8, 9].

A study done by Takako yanai et al [10] proved that both doses of 10 mg and 5 mg olanzapine provided a significant improvement in delayed emesis and a low dose of 5 mg olanzapine was determined as the recommended dose for further phase 3 studies based on higher response rates and lower somnolence rates. Olanzapine was administrated at a dose of 10 mg in most of the previous studies that investigated its antiemetic effect [11-15]. Tan et al. reported that somnolence occurred in 73 % of patients that received olanzapine at dose of 10 mg [13]. While several studies have evaluated the antiemetic effect of olanzapine at a lower dose of 5 mg, there have been few reports published with detailed information relating to adverse events at this dose [9, 16]. When single day chemotherapy is used single-day CT two phases of chemotherapy induced nausea and vomiting have been identified: an acute phase, usually beginning immediately after CT administration and resolving within about 24 h and a delayed phase, defined as starting 24 or more hours after CT and lasting for up to
120 h or more depending on the CT regimen used [17].
 
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