| CTRI Number |
CTRI/2024/08/072429 [Registered on: 13/08/2024] Trial Registered Prospectively |
| Last Modified On: |
18/04/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
A study to find which drug (metoclopramide, thalidomide, prochlorperazine, or lorazepam) is best to treat vomiting due to chemotherapy in patients with cancer. |
|
Scientific Title of Study
|
An open-label phase III randomized controlled trial comparing metoclopramide, thalidomide, prochlorperazine, and lorazepam for treating breakthrough chemotherapy-induced nausea and vomiting in patients receiving olanzapine as part of antiemetic prophylaxis for highly emetogenic chemotherapy. |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Venkatraman Radhakrishnan |
| Designation |
Professor Medical Oncology |
| Affiliation |
Cancer Institute (W.I.A) |
| Address |
Department of Medical Oncology, Cancer Institute (W.I.A), Canal Bank Road, Adyar, Chennai
Chennai
TAMIL NADU
600020
India |
| Phone |
9498082771 |
| Fax |
|
| Email |
venkymd@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Venkatraman Radhakrishnan |
| Designation |
Professor Medical Oncology |
| Affiliation |
Cancer Institute (W.I.A) |
| Address |
Department of Medical Oncology, Cancer Institute (W.I.A), Canal Bank Road, Adyar, Chennai
TAMIL NADU
600020
India |
| Phone |
9498082771 |
| Fax |
|
| Email |
venkymd@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Venkatraman Radhakrishnan |
| Designation |
Professor Medical Oncology |
| Affiliation |
Cancer Institute (W.I.A) |
| Address |
Department of Medical Oncology, Cancer Institute (W.I.A), Canal Bank Road, Adyar, Chennai
TAMIL NADU
600020
India |
| Phone |
9498082771 |
| Fax |
|
| Email |
venkymd@gmail.com |
|
|
Source of Monetary or Material Support
|
| Cancer Institute (W.I.A), Canal Bank Road, Adyar, Chennai, India, 600020 |
|
|
Primary Sponsor
|
| Name |
Cancer Institute WIA |
| Address |
Cancer Institute (W.I.A), Canal Bank Road, Adyar, Chennai, India, 600020 |
| Type of Sponsor |
Other [Trust 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 Venkatraman Radhakrishnan |
Cancer Institute (W.I.A) |
Department of Medical Oncology, Cancer Institute (W.I.A),Canal Bank Road, Adyar, Chennai, India, 600020
Chennai
TAMIL NADU |
9498082771
venkymd@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Cancer Institute (W.I.A) |
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 |
| Intervention |
Lorazepam |
Tab. Lorazepam 0.5 mg per oral every 6 hours for 3 days |
| Comparator Agent |
Metoclopramide |
Tab. Metoclopramide 10 mg per oral every 8 hours for 3 days. |
| Intervention |
Prochlorperazine |
Tab. Prochlorperazine 5 mg per oral every 8 hours for 3 days |
| Intervention |
Thalidomide |
Tab. Thalidomide 50 mg per oral every 12 hours for 3 days. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Age between 18 to 80 years and diagnosed with cancer.
2. Patients with solid malignancies receiving single-day HEC with 4 drug (OPDF) antiemetic prophylaxis.
3. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
4. Women enrolled in the trial need to have a negative pregnancy test within seven days of enrollment and continue to practice contraception during the study period.
5. Patients with breakthrough vomiting and/or ESAS nausea score more than 3 which occur within 5 days of chemotherapy administration.
6. Written informed consent before enrollment.
|
|
| ExclusionCriteria |
| Details |
1. Pediatric patients (age less than 18 years).
2. Patients receiving lorazepam, thalidomide, prochlorperazine, or metoclopramide for other conditions.
3. Patients receiving multi-day chemotherapy in a chemotherapy block.
4. Patients with brain metastasis.
5. Patients receiving abdominal radiotherapy.
6. Patients in whom there are contraindications for the use of thalidomide, metoclopramide, prochlorperazine, or lorazepam like acute narrow-angle glaucoma, respiratory depression, sleep apnea, gastrointestinal hemorrhage, mechanical obstruction, or perforation.
7. History of allergy to any of the drugs used for anti-emetic prophylaxis.
8. Concomitant use of another benzodiazepine, opioids, or antipsychotics other than olanzapine during the protocol therapy.
9. Known cardiac arrhythmia, uncontrolled congestive heart failure, or acute myocardial infarction within the previous six months.
10. History of neurological disorders including seizures and stroke within the last 6 months.
11. History of gastric outlet or intestinal obstruction; severe electrolyte disorder; history of symptomatic thrombosis; history or suspected likelihood of using narcotic analgesics; inability to take or absorb oral medicine.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The number of patients with no episodes of vomiting after the use of rescue medication (CR) during 0 to 72 hours. |
3 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| The number of patients with CR to nausea (score of 0 on the ESAS scale) during 0 to 72 hours after starting rescue antiemetic. |
3 days |
| Comparison of toxicities among the four regimens. |
5 days |
| Assessing patient-reported outcomes using the MD Anderson Symptom Inventory (MDASI). |
5 days |
|
|
Target Sample Size
|
Total Sample Size="200"
Sample Size from India="200"
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)
|
01/09/2024 |
| 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="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Chemotherapy-induced nausea and vomiting (CINV) is the most common and distressing side-effect of chemotherapy administration. CINV occurs in 30-40% of patients receiving highly emetogenic chemotherapy (HEC) despite adequate anti-emetic prophylaxis. The current standard of care for HEC is 4 drug regimen with olanzapine, 5-HT3 antagonist (eg: palonosetron), dexamethasone and NK1 antagonist (eg: fosaprepitant). Breakthrough CINV is defined as vomiting and/or nausea that occurs within five days of chemotherapy administration after the use of guideline-directed prophylactic antiemetic agents. The National Comprehensive Cancer Network (NCCN) guidelines suggest treating breakthrough CINV with an agent from a drug class that was not used in the prophylactic regimen and recommend continuing the breakthrough medication if nausea and vomiting are controlled. The Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) guidelines suggest that when breakthrough emesis occurs, the prophylactic regimen for subsequent cycles should be changed by switching to a different 5-HT3 antagonist, substituting metoclopramide for the 5-HT3 receptor antagonist, or adding other agents such as dopamine antagonists or benzodiazepines. However, they do not provide a specific recommendation for treating breakthrough CINV. The American Society of Clinical Oncology (ASCO) 2020 anti-emetic guidelines suggest that adults experiencing nausea and/or vomiting despite optimal prophylaxis, and who have already used olanzapine, may be offered an NK1R antagonist, lorazepam, alprazolam, a dopaminergic antagonist (e.g., prochlorperazine, thiethylperazine, haloperidol), or an alternative type of 5-HT3 antagonist than was administered initially. Naveri et al. conducted a double-blind randomized phase III trial for breakthrough CINV in patients receiving HEC, comparing olanzapine and metoclopramide. In this study, patients had not received olanzapine in prophylaxis. Olanzapine was found to be superior to metoclopramide for treating breakthrough CINV. Lorazepam, prochlorperazine, and metoclopramide are recommended as rescue antiemetics by the NCCN for treating breakthrough emesis. Metoclopramide has been shown to be inferior to olanzapine for treating breakthrough CINV. However, current antiemetic regimens recommend olanzapine for prophylactic use, precluding its use for treating breakthrough CINV. There are no phase 3 randomized controlled trials assessing the safety and efficacy of lorazepam and prochlorperazine for treating breakthrough CINV. Thalidomide is not included in guidelines for treating breakthrough CINV, despite its demonstrated efficacy and safety as an antiemetic for CINV prophylaxis in recent years. No trials have compared lorazepam, thalidomide, prochlorperazine, and metoclopramide in patients receiving olanzapine as antiemetic prophylaxis. In the era of olanzapine prophylaxis, the efficacy of rescue antiemetics remains unknown. Therefore, we plan to study the efficacy of lorazepam, thalidomide, prochlorperazine, and metoclopramide as rescue antiemetics for breakthrough CINV.
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