| CTRI Number |
CTRI/2023/12/060941 [Registered on: 29/12/2023] Trial Registered Prospectively |
| Last Modified On: |
27/12/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Using medicine Fosaprepitant along with other anti-vomiting medications for better control of vomiting and nausea in children receiving chemotherapy |
|
Scientific Title of Study
|
Anti-Emetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting with Fosaprepitant for Children and Adolescents Receiving Moderately Emetogenic Chemotherapy: An Investigator-Initiated, Double-blinded, Superiority, Phase III Randomized Controlled Trial. |
| Trial Acronym |
CIVIC MAN |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Prasanth Srinivasan |
| Designation |
Assistant Professor |
| Affiliation |
Department of Medical Oncology, Division of Pediatric Oncology, Cancer Institute (WIA) |
| Address |
Room No: 2, CHW - Third Floor, Dr. VS Campus, Adyar
Chennai
TAMIL NADU
600020
India |
| Phone |
9790093486 |
| Fax |
|
| Email |
prasanth230591@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Prasanth Srinivasan |
| Designation |
Assistant Professor |
| Affiliation |
Department of Medical Oncology, Division of Pediatric Oncology, Cancer Institute (WIA) |
| Address |
Room No:2, CHW - Third Floor, Dr. VS Campus, Adyar
Chennai
TAMIL NADU
600020
India |
| Phone |
9790093486 |
| Fax |
|
| Email |
prasanth230591@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Prasanth Srinivasan |
| Designation |
Assistant Professor |
| Affiliation |
Department of Medical Oncology, Division of Pediatric Oncology, Cancer Institute (WIA) |
| Address |
Room No:2, CHW - Third Floor, Dr. VS Campus, Adyar
Chennai
TAMIL NADU
600020
India |
| Phone |
9790093486 |
| Fax |
|
| Email |
prasanth230591@gmail.com |
|
|
Source of Monetary or Material Support
|
| Cancer Institute (WIA)
Dr. VS Campus, Adyar, Chennai, Tamil Nadu, India |
|
|
Primary Sponsor
|
| Name |
Cancer Institute (WIA) |
| Address |
Dr. VS Campus, Adyar, Chennai, Tamil Nadu, India |
| 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 Prasanth Srinivasan |
Cancer Institute (WIA) |
Room No:2, CHW - Third Floor, Division of Pediatric Oncology, Department of Medical Oncology, Dr. VS Campus, Adyar
Chennai
TAMIL NADU |
9790093486
prasanth230591@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Cancer Institute (WIA) - Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C910||Acute lymphoblastic leukemia [ALL], |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Fosaprepitant, Palonosetron and Dexamethasone |
1. Fosaprepitant
• 12-18 years: 150 mg IV over 30 minutes.
• 4 years-less than 12 years: 4 mg/kg (maximum dose 150 mg) intravenously over 60 minutes.
2. Palonosetron. 4 to 17 years: 0.02 mg/kg/dose (maximum 1.5 mg) IV infusion once.
17–18 years: 0.25 mg IV push slowly.
3. Dexamethasone 7 mg/m2/day (3.5 mg/m2/dose) IV/PO q12 hourly (Rounded to nearest 0.5 mg for tablets) for 48 hours after fosaprepitant administration.
Followed by 7 mg/m2/day (3.5 mg/m2/dose) IV/PO q 12 hourly for 72 hours (3 days) of delayed period.
|
| Comparator Agent |
Placebo, Palonosetron and Dexamethasone |
1. Placebo – Normal saline
2. Palonosetron. 4 to 17 years: 0.02 mg/kg/dose (maximum 1.5 mg) IV infusion once.
17–18 years: 0.25 mg IV push slowly.
3. Dexamethasone 14 mg/m2/day (7 mg/m2/dose) IV/PO q12 hourly (Rounded to nearest 0.5 mg for tablets) till completion of the acute period. Followed by 7 mg/m2/day (3.5 mg/m2/dose) IV/PO q 12 hourly for 72 hours (3 days) of delayed period.
|
|
|
Inclusion Criteria
|
| Age From |
4.00 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
1. Age between 4 to 18 years and diagnosed with cancer. Patients under four years have not been included as nausea assessment cannot be performed.
2. Receiving single-day regimen of moderately emetogenic chemotherapy (MEC).
3. Patients could have received prior chemotherapy. They need not be chemotherapy naïve.
4. Lansky play performance score of 60 or more for less than 16 years. Eastern Cooperative Oncology Group performance status of 0, 1, or 2 for 16-18 years.
5. Adequate organ function as confirmed by laboratory investigations within two weeks [Aspartate transaminase (AST) and Alanine transaminase (ALT) within four times upper limit of normal (ULN), serum bilirubin less than 2 mg/dL, serum creatinine within ULN].
6. Written informed consent from parents before enrollment. Children above 7-12 years of age will need to provide verbal assent. Children between 13 and 18 years of age must provide written assent.
|
|
| ExclusionCriteria |
| Details |
1. Benzodiazepines or opioids are initiated 48 hours before treatment, except for single doses of triazolam, temazepam, or midazolam.
2. History of vomiting 24 hours before enrollment.
3. Use of antiemetics within 48 hours before treatment.
4. Patients receiving corticosteroids as a part of their chemotherapy protocol.
5. Patients with a primary brain tumor or brain metastasis.
6. Patients receiving concurrent radiotherapy with chemotherapy.
7. Patients in whom there are contraindications for corticosteroid use like uncontrolled diabetes mellitus, uncontrolled hypertension, active peptic ulcer disease and gastrointestinal bleeding.
8. History of allergy to any of the drugs used for anti-emetic prophylaxis.
9. Pregnant or breastfeeding patients.
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 1. To estimate and compare the proportion of patients with complete response (CR) for vomiting during the overall period between triple drug regimen (DPF) and two drug regimen for CINV prophylaxis (DP). |
0-120 hrs |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| 1. To compare the proportion of patients with complete response (CR) rates for vomiting during the acute period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis. |
0-24 hrs |
| 2. To compare the proportion of patients with complete response (CR) rates for vomiting during the delayed period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis |
24-120 hrs |
| 3. To compare the proportion of patients with CR to nausea for the overall, acute and delayed period period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis. |
0-120 hrs |
| 4. To compare the grade 3 and grade 4 toxicities between the two regimens |
0-120 hrs |
|
|
Target Sample Size
|
Total Sample Size="192"
Sample Size from India="192"
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)
|
01/02/2024 |
| 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="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Informed Consent Form
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - For individual participant data meta-analysis.
- By what mechanism will data be made available?
Response - Proposals should be directed to [prasanth230591@gmail.com].
- For how long will this data be available start date provided 27-06-2027 and end date provided 27-01-2031?
Response - Beginning 9 months and ending 36 months following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - Nil
|
|
Brief Summary
|
Review of Literature: The recently published clinical practice guidelines (CPG) for prevention of acute and delayed CINV in pediatric cancer patients strongly recommends the combination of 5-Hydroxytryptamine receptor antagonist (5HT3RA) and dexamethasone to prevent acute phase CINV among children receiving moderately emetogenic chemotherapy (MEC). However, this recommendation is based on meta-analysis of 3 randomised controlled trials (RCTs) among adult patients comparing 5HT3RA and dexamethasone with 5HT3RA alone (RR 1.29, 95% CI: 1.21–1.39). Based on the meta-analysis of 11 RCTs comprising of no pediatric patients, the recent CPG concluded that triple drug prophylaxis with 5HT3RA, dexamethasone, and neurokinin-1 (NK-1) antagonist provided no added benefit compared with dual agent (5HT3RA and dexamethasone) prophylaxis in acute phase CIV control (RR 1.03, 95% CI: 1.00–1.07) or acute phase CIN control (RR 1.02, 95% CI: 0.91–1.16). This is in contrary to the results of a subgroup analysis of our previous trial which compared three drug (ondansetron, dexamethasone and fosaprepitant) with two drug (ondansetron and dexamethasone) anti-emetic prophylaxis for children receiving MEC [CR rate of acute CINV: 92% vs 67%; (p value = 0.001)]. Rationale for the study: · After the review of literature, we identified the lacunae of pediatric specific data supporting the recommendation of anti-emetic prophylaxis for children receiving MEC. Despite the guideline consistent anti-emetic prophylaxis with Dexamethasone and 5HT3 RA, 30-40% of patients receiving MEC still experience breakthrough vomiting. Aprepitant and Fosaprepitant are the other potent anti-emetic agents, which has shown its efficacy in children receiving HEC. Since the recommended doublet anti-emetic prophylactic regimen has not reduced the incidence of CINV to the desirable level of <10%, we propose to study the benefit of adding Fosaprepitant to the standard two drug prophylaxis among children receiving MEC. This study may help to optimize the anti-emetic prophylaxis for children receiving MEC, thereby ensuring emesis free chemotherapy delivery. This study may contribute to the pediatric specific evidence required for formulating the CINV prophylactic guidelines for children. RESEARCH QUESTION
|