Study to Evaluate Anti-emetic Effect of Aprepitant Versus Placebo in Children and Adolescent Receiving Chemotherapy (Aprepitant)

A Study to Evaluate the Anti-emetic Effect of Aprepitant Versus Placebo as an Add-on Therapy in Children and Adolescent Receiving Chemotherapy: A Randomized, Doubly Blinded Controlled Trial

Chemotherapy induced nausea and vomiting (CINV) is one of the few mostly observed distressing toxicity of cancer treatment. It can occur up to 90% in case of highly emetogenic chemotherapy use. CINV causes disturbance in daily living of cancer patient and reduces compliance with treatment Even with the standard anti-emetic measures up to 50% patient can suffer from this complication. Whereas there is standard anti-emetic guideline exists in case of adult patients, there no such guidelines made in pediatric population. The new drug Aprepitant has been recommended for use in adults with high efficacy, there no such concrete data available in children regarding its use. There are few retrospective reports and limited data available regarding use of Aprepitant in children with satisfactory efficacy in reducing CINV. As there no randomized large data to suggests its efficacy and its routine use in children, we have planned this study.

Study Overview

• Status: Completed
• Conditions: Chemotherapy Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Aprepitant; Drug: Placebo

Detailed Description

Population:

Children and adolescents (5-18 years) with weight between 15-65 kg receiving highly emetogenic chemotherapy (HEC) -

• VAC (vincristine, dactinomycin/Adriamycin, cyclophosphamide)
• ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
• Cisplatin/Doxorubicin

Sampling technique Subjects who met the eligibility criteria will be randomly assigned using random allocation number generated by computer into one of the two groups. The unit of randomization will be the subject at first cycle of HEC. The same patient will not be enrolled for twice

Procedure for data collection:

1. The data will be collected from each patient from d1 to d10 of chemotherapy of which patient will received chemotherapy in day care, maximum up to d3.
2. After taking consent patient will be enrolled as per inclusion and exclusion criteria, and randomized to one of two groups. All baseline assessment will be done. Patient will be explained about the filling of the diary. In first 2 days. The subjects will fill the diary under the investigator supervision, and the rest of filling will be in home. Reinforcement will be done over phone.

Procedure of double blinding

• Double blinding will be done for the intervention. Four different boxes will be made for capsules. Total 3 capsules for 3 days will be made in a blister pack, mentioning the d1, d2, d3 (for each capsule). Two different body weight groups will be made: 15-40 kg, and 41-65 kg.
• Group "A" will be the code for Aprepitant group and group "B" will be code for control group. Both patient and the investigator will be blinded regarding medicine in the code.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Dr. BRA IRCH, AIIMS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All subjects must have a confirmed diagnosis of malignancy and receiving highly emetogenic chemotherapy first time (VAC, ABVD and CDDP/Doxorubicin)
• Age group 5-18 years with weight between 15-65 kg
• Children/adolescents and their caregiver who can understand Hindi or English and willing to participate in the study (with written informed consent)

Exclusion Criteria:

• Significant organ dysfunction
• Active infection
• Pregnancy
• Uncontrolled medical condition other than malignancy
• Need for contraindicated concomitant medication
• Patients receiving chemotherapy other than VAC, ABVD and CDDP/Doxorubicin
• Treatment with another investigational drug within 4 weeks of study start or prior Aprepitant use
• Had received or will receive RT to abdomen or pelvis in the week prior to treatment
• Vomited in the 24 hr prior to treatment
• Prior exposure to highly emetogenic chemotherapeutics
• Abnormal lab values (ANC<1500/mm3, TLC<3000/mm3, Plt<100,000/mm3, AST/ALT> 2.5 times of ULN, bill>1.5 times of ULN, S.cr>1.5 times of ULN, patient on systemic steroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aprepitant; It is an double blind randomized placebo controlled trial with age group of 5-18 years and weight between 15-65 kg, who will receive highly emetogenic chemotherapy. Patient who will meet the inclusion criteria will be randomly enrolled in either of the two arm-aprepitant arm and control arm. The patient on aprepitant arm will receive the study drug (aprepitant)along with standard anti-emetic therapy (as per the dosages mentioned in the protocol).	Drug: Aprepitant; The patient on study group with weight category of 15-40 kg will receive: D1- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 80 mg; D2- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 80 mg; D3- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 80 mg and The patient with weight category of 41-65 kg in study group will receive: D1- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 125 mg; D2- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 80 mg; D3- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant 80 mg; Other Names: Empov
Placebo Comparator: Control; It is an double blind randomized placebo controlled trial with age group of 5-18 years and weight between 15-65 kg, who will receive highly emetogenic chemotherapy. Patient who will meet the inclusion criteria will be randomly enrolled in either of the two arm-aprepitant arm and control arm. The patient on the control arm will receive the placebo along with standard anti-emetic therapy (as per the dosages mentioned in the protocol).	Drug: Placebo; Patient on control group with weight category of 15-40 kg will receive: D1- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 80 mg; D2- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 80 mg; D3- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 80 mg; and The patient on control group with weight category of 41-65 kg will receive: D1- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 125 mg; D2- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 80 mg; D3- Dexamethasone 0.15 mg/kg, ondansetron (0.15 mg/kg, single dose), Aprepitant placebo 80 mg (all are injectable except Aprepitant oral capsule).; Other Names: Empov placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
- Numbers of episodes of nausea and vomiting. - Duration of nausea (in hours). - Severity of nausea as per Edmonton's Symptom Assessment System (ESAS), numerical scale for nausea.	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
- Chemotherapy induced additional side effects. - Number of anti-emetic dosage (other than aprepitant) required for treatment of vomiting.	5 days

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, New Delhi
• Collaborators: Dr. Reddy's Laboratories Limited
• Investigators: Principal Investigator: Sameer Bakhshi, MD, Dr. BRA IRCH, AIIMS, New Delhi (India)

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 26, 2011

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 16, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: CT/38/011/RS