PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-i… (NCT03204279) | Clinical Trial Compass
CompletedPhase 2
PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting
United States, Russia, Serbia67 participantsStarted 2017-08-31
Plain-language summary
This study is Phase 2 pharmacokinetic (PK) and pharmacodynamic (PD) dose-finding study of oral netupitant administered concomitantly with oral palonosetron in pediatric cancer patients for the prevention of nausea and vomiting associated with emetogenic chemotherapy. Two different netupitant dosages will be tested in patients aged from 3 months to \< 18 years: 1.33 mg/kg up to a maximum of 100 mg, and 4 mg/kg up to a maximum of 300 mg. All netupitant doses in all age classes will be concomitantly administered with palonosetron 20 μg/kg (up to a maximum dose of 1.5 mg) which is the IV palonosetron dose approved by USA FDA for the pediatric population. The primary objective is to investigate the PK/PD relationship between netupitant exposure (AUC, Cmax) and antiemetic efficacy (CR in delayed phase) after a single oral netupitant administration, concomitantly with oral palonosetron in pediatric cancer patients receiving Moderately Emetogenic Chemotherapy (MEC) or Highly Emetogenic Chemotherapy (HEC) cycles. Efficacy parameter to be used in the correlation is the proportion of patients with Complete Response (CR i.e., no emetic episodes and no rescue medication) during (\> 24-120 h after the start of chemotherapy on Day 1).
The secondary objectives are to assess the safety and tolerability after single oral administration of netupitant given concomitantly with a single oral administration of palonosetron; to evaluate the pharmacokinetic (AUC, Cmax, tmax and t1/2) of oral palonosetron at the fixed dose of 20 μg/kg in pediatric patients with the concomitant administration of netupitant. A total of 92 pediatric cancer patients receiving either HEC or MEC will be enrolled in the study.
Who can participate
Age range
17 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Signed written informed consent by parent(s)/legal guardians of the pediatric patient in compliance with the local laws and regulations. In addition signed children's assent form according to local requirements.
. Male or female in- or out-patient from birth to \< 18 years at the time of randomization.
. Patient weight at least 3.3 kg.
. Naïve or non-naïve patient with histologically, and/or cytologically (or imaging in the case of brain tumors) confirmed malignant disease.
. Scheduled and eligible to receive at least one moderately or highly emetogenic chemotherapeutic agent on Day 1 only or for multiple days.
. For patient aged ≥ 10 years: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant
Timeframe: within 168 hours after netupitant administration. A sampling windows approach will be used by collecting a single blood sample from each patient in one of these time windows: from 2 to 8 h, from 24 to 48 h, from 72 to 96 h and from 120 to 168 h.
2
Maximum Plasma Concentration (Cmax) of Netupitant
Timeframe: within 168 hours after netupitant administration. A sampling windows approach will be used by collecting a single blood sample from each patient in one of these time windows: from 2 to 8 h, from 24 to 48 h, from 72 to 96 h and from 120 to 168 h
3
Exposure - Response Analysis for Netupitant
Timeframe: > 24-120 hours after the start of chemotherapy on Day 1
. For patient aged 2 years with known mild to moderate hepatic impairment: in the Investigator's opinion the impairment does not jeopardize patient's safety during the study.
. For patient aged 2 years with known mild to moderate renal impairment: in the Investigator's opinion the impairment should not jeopardize patient's safety during the study.
Exclusion criteria
. The patient and/or parents/caregivers are expected by the Investigator to be non-compliant with the study procedures.
. Patient has received or is scheduled to receive total body irradiation, total nodal irradiation, upper abdomen radiotherapy, half or upper body irradiation, radiotherapy of the cranium, craniospinal regions, head and neck, lower thorax region or the pelvis within 1 week prior to study entry (Day 1) or within 120 h after start of chemotherapy administration on Day 1.
. Known history of allergy to any component or other contraindications to any Neurokinin-1 (NK1) or 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
. Active infection.
. Uncontrolled medical condition (e.g., uncontrolled insulin dependent diabetes mellitus).
. Patient suffering from ongoing vomiting from any organic etiology (including patients with history of gastric outlet obstruction or intestinal obstruction due to adhesions or volvulus, patients with a symptomatic central nervous system(CNS) tumor causing nausea and/or vomiting) or patient with hydrocephalus.
. Patient who experienced any vomiting, retching, or nausea within 24 h prior to the administration of the study drug
. Patient who received any drug with potential anti-emetic effect within 24 h prior to the start of reference chemotherapy, including but not limited to: