| 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
|
|
|
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
|
|
|
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]. |