| CTRI Number |
CTRI/2018/12/016643 [Registered on: 13/12/2018] Trial Registered Prospectively |
| Last Modified On: |
11/12/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
olanzipine antiemtic study |
|
Scientific Title of Study
|
A randomized, open label, parallel-group, phase 3 study to investigate the efficacy and tolerability of palonosetron, dexamethasone, aprepitant plus Olanzapine versus palonosetron, dexamethasone and aprepitant alone in patients receiving high moderately emetogenic chemotherapeutic (MEC) regimens (OMEC study) |
| Trial Acronym |
OMEC |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| protocol version 2.0 16 aug 2018 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Vikas ostwal |
| Designation |
Associate professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
11th Floor Room Number 1102 homibhaba building Dr Ernest Borges Marg parel mumbai 400012
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9702288801 |
| Fax |
|
| Email |
dr.vikas.ostwal@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Vikas ostwal |
| Designation |
Associate professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
11th Floor Room Number 1102 homibhaba building Dr Ernest Borges Marg parel mumbai 400012
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9702288801 |
| Fax |
|
| Email |
dr.vikas.ostwal@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Vikas ostwal |
| Designation |
Associate professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
11th Floor Room Number 1102 homibhaba building Dr Ernest Borges Marg parel mumbai 400012
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9702288801 |
| Fax |
|
| Email |
dr.vikas.ostwal@gmail.com |
|
|
Source of Monetary or Material Support
|
| Unrestricted grant from Dr.reddy’s Private limited
Buidling number P/3 (Gala Number 1,2 and 3)
Prithivi complex, kather village
Tal.Bhivandi Dist Thane 421302
|
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Dr Ernest Borges Marg Parel Mumbai |
| Type of Sponsor |
Research institution and hospital |
|
|
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 Vikas Ostwal |
Tata Memorial Hospital |
3rd floor room no 323 homibhaba building Dr ernest Borges Marg Parel Mumbai
Mumbai
MAHARASHTRA |
9702288801
dr.vikas.ostwal@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Commitee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C15-C26||Malignant neoplasms of digestive organs, (2) ICD-10 Condition: C30-C39||Malignant neoplasms of respiratory and intrathoracic organs, (3) ICD-10 Condition: C64-C68||Malignant neoplasms of urinary tract, (4) ICD-10 Condition: C00-C14||Malignant neoplasms of lip, oral cavity and pharynx, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
3 drug antiemetic regimen
include drugs aprepitant,
palonosetron, Dexamethasone
|
Day 1
60 mins before chemotherapy,
capsule aprepitant 125 mg PO plus
palonosetron 0.25mg IV plus
Dexamethasone 12 mg IV
Day 2 and Day 3
capsule aprepitant 80 mg PO
Written Instructions will be given to patient regarding oral intake of capsule Aprepitant for D2 and D3
|
| Intervention |
4 drug antiemetic regimen include drugs
aprepitant, palonosetron,Dexamethasone,
olanzipine |
Day 1
60 mins before chemotherapy,
capsule aprepitant 125 mg PO plus
palonosetron 0.25mg IV plus
Dexamethasone 12 mg IV
Tablet Olanzapine 10 mg PO at night prior to sleep (oral and written instructions will be given to patient)
Day 2 and Day 3
capsule aprepitant 80 mg PO plus
Tablet Olanzapine 10mg PO at night prior to sleep
Oral and written Instructions will be given to patient regarding oral intake of capsule Aprepitant and tablet olanzapine for day 2 and day 3.
|
|
|
Inclusion Criteria
|
| Age From |
19.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
1.Patients has a confirmed diagnosis of one of the cancers mentioned previously and is receiving one of the mentioned chemotherapy protocols mentioned previously.
2.The patient understands the nature and purpose of this study and the study procedures and has signed informed consent.
3.The patient is aged > 18 years.
4.Patients should be chemotherapy naïve.
5.The patient has a WHO Performance Status of ≤1.
6.Hematologic and metabolic status must be adequate for receiving planned chemotherapy, and meet the following criteria:
Total neutrophils ≥ 1500/mm3
Platelets ≥ 100,000/mm3
Bilirubin ≤ 1.5 x ULN (Upper Limits of Normal)
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 x ULN
GFR ≥ 50 ml/min
7. The patient is able to read, understand, and complete questionnaires and daily components of the Patient Diary for each study cycle.
8. For patients of childbearing potential, urine human chorionic gonadotropin (hCG) (urine dipstick pregnancy test) or blood hCG results must be negative at screening.
9. Has a normal baseline ECG with no QTc prolongation
|
|
| ExclusionCriteria |
| Details |
1.The patient is unable to read, understand, and complete the forms required for the study.
2.The patient is pregnant or lactating.
3.The patient has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea (defined as nausea graded as moderate or severe) in the 24 hours preceding the first dose of study medication.
4.The patient has a history active peptic ulcer disease, significant or symptomatic, acute or subacute gastrointestinal obstruction, increased intracranial pressure,severe cognitive impairment, known central nervous system disease (e.g. brain metastases/ a seizure disorder).
5. hypercalcemia, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV) or pose an unwarranted risk to the patient.
6. The patient has a known hypersensitivity or contraindication to palonosetron, another 5-HT3 receptor antagonist, dexamethasone, aprepitant or olanzapine
7.The patient has received an investigational drug in the previous 6 months or is scheduled to receive any investigational drug other than fosaprepitant dimeglumine during the study period
8.The patient has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medications. Opiate drugs for cancer pain will be permitted if the patient has been on a stable dose and has not experienced emesis or clinically significant nausea from the narcotics in the 24 hours preceding the first dose of study medication.
9.The patient has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drugs. This is inclusive of, but not limited to 5 HT3 antagonists, metoclopramide, benzodiazepines, phenothiazines, haloperidol, oral or intravenous steroids, antihistamines, domperidone, olanzapine, antipsychotics.
10.Patient on antipsychotics or being planned to receive any of the antiphychotics, amifostine in last 3 months.
11.Patient has received concurrent abdominal radiotherapy in last 3 months or being planned to receive the same.
12.Patient is receieving or will likey to receive concurrent use of quinolone antibiotic therapy.
13.Patient with the history of chronic alcoholism.
14.Patient with cardiac arrhythmia, uncontrolled/ controlled heart failure, or acute coronary event or uncontrolled diabetes mellitus within the previous 6 months.
15.Has taken drugs which may influence medications used in the study, e.g. CYP inducers or inhibitors. This will have to be evaluated for and decision taken by PI
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Objectives The primary objective is to compare an antiemetic regimen consisting of aprepitant, palonosetron, dexamethasone and olanzapine (active arm) and a regimen consisting of aprepitant, palonosetron, and dexamethasone, (control arm) with respect to complete response (CR); the proportion of subjects with no vomiting, no significant nausea (scored as 5 on a scale of 1-100) and no use of rescue medications during pre-specified high MEC protocols for 1 cycle of chemotherapy |
42 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1.To compare the olanzapine containing regimen to the control arm with respect to no emesis rates
2.to compare the olanzapine containing regimen to the control arm with respect to proportion of patients with no significant nausea 3.olanzapine containing regimen to the control arm with respect to CR rates 4.FLIE questionnaire 5.tolerance and side effects with both regimens |
42 months |
|
|
Target Sample Size
|
Total Sample Size="560"
Sample Size from India="560"
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
|
Phase 3 |
|
Date of First Enrollment (India)
|
18/12/2018 |
| 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="3"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
not yet published |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Study rationale Chemotherapy induced nausea and vomiting (CINV) are unpleasant and worrisome side effects associated with the administration of chemotherapy. Improved control of emesis positively impacts quality of life in patients receiving chemotherapy and lack of adequate control also reflects adversely on quality of life (1). While current antiemetic regimens have markedly reduced the incidences of vomiting across chemotherapy regimens, control of nausea has not been as effective with lesser importance also having been given to this equally important and distressing side effect(2,3). The term ‘Moderately emetogenic chemotherapy (MEC)’ is a mixed bag of regimens with varying incidences of CINV (30%-90%) with currently used antiemetic regimens. The currently approved antiemetic regimen for MEC is the combination of a 5 HT3 antagonist and dexamethasone, with the exception of regimens using carboplatin AUC >4, where the addition of a neurokinin (NK)1-receptor antagonist (RA) is recommended(4,5). Besides Carboplatin, other chemotherapeutic agents which may be considered to have high to moderate emetogenic potential include Irinotecan and Irinotecan based combination regimens(6). The addition of NK1-RA antagonists has improved complete response rates in HEC and MEC regimens - however, 20% - 38% of patients still do not achieve complete response (CR)(7,8). Beyond not achieving CR, a majority of the seminal clinical trials have not concentrated on control of nausea. While acute, and to a certain extent delayed vomiting control rates have improved, control of nausea still remains low. The lack of control of nausea is one of the major reasons for a lag between control of vomiting and CR rates for nausea and vomiting. Olanzapine is one of the recommended drugs for use in highly emetogenic chemotherapy (HEC) regimens (9,10). Known as an atypical antipsychotic agent of the thiobenzo-diazepine class, olanzapine was approved by the USA FDA (Food and Drug Administration) for the treatment of the manifestations of psychotic disorders in 1996. Olanzapine blocks multiple neurotransmitter receptors including dopaminergic D1, D2, D3,
D4 brain receptors, serotonergic 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamine alpha1 adrenergic receptors, acetylcholine muscarinic receptors, and histamine H1 receptors. Moreover, olanzapine may reduce opioid requirements in cancer patients with uncontrolled pain, cognitive impairment, or anxiety. Due to the broad and potent inhibitory activity of olanzapine at multiple receptors involved in the nausea and vomiting pathways, this agent is an effective treatment as well as prophylaxis for CINV. It is also a significant inhibitory effect on nausea from available data. Besides its efficacy in CINV, it is also a low cost medication with a tolerable safety profile. Side effects may include mild short-term sedation, as well as weight gain and an increased risk of diabetes mellitus with prolonged use (>6 months). The efficacy of Olanzapine has been shown in small Phase 2 and retrospective studies when used as an additional antiemetic in MEC(11–13). However, there is no phase 3 study examining the role of olanzapine in MEC. The purpose of this study is therefore to investigate in a randomized manner, if the addition of Olanzapine to the combination of a 5-HT3-RA (palonosetron) plus a corticosteroid (dexamethasone) and NK1-RA improves the antiemetic efficacy in patients receiving specific ‘high’ MEC regimens. The assessment of quality of life in cancer patients as per patient reported outcomes of a treatment sometimes differ in comparison with the clinical objective outcome. Keeping this in mind, we will also investigate the patient reported outcomes with respect to nausea and vomiting. As part of this, the Functional Living-Index Emesis (FLIE) questionnaire will be used as part of the study. primary hypothesis The addition of Olanzapine to palonosetron, dexamethasone and aprepitant combination will increase the CR rates [(the proportion of subjects with no vomiting, no significant nausea (scored as < 5 on a scale of 1-100) and no use of rescue medications] during high MEC regimens. |