E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Study to evaluate the efficacy and safety of two different doses of palonosetron compared to ondansetron in the prevention of CINV in pediatric patients undergoing single and repeated cycles of MEC or HEC |
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E.1.1.1 | Medical condition in easily understood language |
prevention of chemotherapy induced nausea and vomiting |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049091 |
E.1.2 | Term | Chemotherapy antiemetic prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036899 |
E.1.2 | Term | Prophylaxis against chemotherapy induced vomiting |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of two different doses of IV palonosetron in the prevention of chemotherapy induced nausea and vomiting in MEC and HEC patients through 120 hours after start of chemotherapy in single and repeated chemotherapy cycles. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of IV palonosetron in pediatric patients.
• To evaluate the pharmacokinetics of IV palonosetron in a subset of pediatric CINV patients.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Open label neonate sub-study dd. 25 MAR 2011
For neonates (< 28 days, full term) a preliminary open-label sub-study will be carried out. First the lower dose of 3 mcg/kg will be tested to assess the safety and tolerability of palonosetron.
Pharmacokinetic sub-study dd. 25 MAR 2011
Patients selected for the PK sub-study will undergo PK sampling at regular visits and will have one additional visit for the collection of PK samples. |
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E.3 | Principal inclusion criteria |
1. Written informed consent signed 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.
2. Male or female in- or out-patients from neonates (full term) to <17 years at the time of randomization.
3. Patient weight at least 3.2 kg.
4. Histologically, and/or cytologically (or imaging in the case of brain tumors) confirmed malignant disease.
5. Naïve or non-naïve to chemotherapy.
6. Scheduled and eligible to receive at least one of the moderately or highly emetogenic chemotherapeutic agents on Study Day 1.
7. For patients aged ≥ 10 years to <17 years: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 .
8. For patients with known hepatic impairment (defined as AST > 2.5 ULN or ALT > 2.5 ULN or total bilirubin > 1.5 ULN): in the Investigator’s opinion the impairment should not jeopardize patient’s safety during the study.
9. For patients with known renal impairment (defined as creatinine >1.5 ULN): in the Investigator’s opinion the impairment should not jeopardize patient’s safety during the study.
10. For patients with known history or predisposition to cardiac abnormalities: in the Investigator’s opinion the history/predisposition should not jeopardize patient’s safety during the study.
11. For patients with known clinically relevant abnormal laboratory values: in the Investigator’s opinion the abnormality should not jeopardize the patient’s safety during the study.
12. Fertile patients (male or female) must use reliable contraceptive measures (such measures, for patients and sexual partners, include: implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized/sterilized partner, use of a double-barrier method or sexual abstinence).
13. Female patients who have attained menarche must have a negative pregnancy test at the screening visit (Visit 1) and at study treatment visit (Visit 2). The patient and her parent(s) must be counseled on the importance of not becoming pregnant before or during the study.
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E.4 | Principal exclusion criteria |
1. The patient and/or parents/caregivers are expected by the Investigator to be non-compliant with the study procedures.
2. Lactating or pregnant female patient.
3. Patient has received total body irradiation, upper abdomen radiotherapy, radiotherapy of the cranium, craniospinal regions or the pelvis within 1 week prior to study entry (screening).
4. Scheduled to receive concomitant total body irradiation, radiotherapy of the upper abdomen, lower thorax region, or cranium/craniospinal regions up to 24 hours after study drug administration.
5. Known history of allergy to any component or other contraindications to any 5-HT3 receptor antagonists.
6. Active infection.
7. Uncontrolled medical condition (e.g., uncontrolled insulin-dependent diabetes mellitus).
8. Marked baseline prolongation of QTc interval [QTcB or QTcF > 460 msec] in any of the ECG assessments at screening. For this purpose, assessment will rely on the automatic interpretation by the ECG machine.
9.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) or patients with hydrocephalus.
10. Patient who experienced any vomiting, retching, or nausea within 24 hours prior to the administration of the study drug.
11. Patient who received any drug with potential anti-emetic effect within 24 hours prior to administration of study treatment, including but not limited to:
•NK1- receptor antagonists (e.g. aprepitant)
•5-HT3 antagonists (e.g., ondansetron, granisetron, dolasetron);
•Phenothiazines (e.g., perphenazine, prochlorperazine, promethazine, fluphenazine, chlorpromazine, thiethylperazine);
•Butyrophenones (e.g., droperidol, haloperidol);
•Benzamides (e.g., metoclopramide, alizapride);
•Corticosteroids (e.g., prednisone, methylprednisolone; except inhaled steroids for respiratory disorders and topical steroids for skin disease with doses of ≤ 10 mg of prednisone daily or its equivalent); Corticosteroids foreseen in the chemotherapy regimen or to reduce intracranial pressure are allowed. According to the guidelines1,2, patients will receive also dexamethasone as a co-medication in accordance with standard clinical practice and if deemed appropriate by the Investigator.
•Dimenhydrinate; Hydroxyzine; Domperidone; Lorazepam; Cyclizine; Cannabinoids; Scopolamine; Trimetobenzamide HCl; Meclizine hydrochloride; Pseudoephedrine HCl;
•Over the Counter (OTC) antiemetics, OTC cold or OTC allergy medications;
•Herbal preparations containing ephedra or ginger.
12. Patient aged ≤ 6 years who received any investigational drug (defined as a medication with no marketing authorization granted for any age group and any indication) within 90 days prior to Day 1, or patient aged > 6 years who received any investigational drug within 30 days prior to Day 1 or is expected to receive investigational drugs prior to study completion.
13.Patient who participated in any previous trial with palonosetron.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients showing Complete Response (CR) defined as no vomiting, no retching and no use of antiemetic rescue medication in the acute phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from 0-24 hours (acute phase) after start of chemotherapy (T0) during first cycle |
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E.5.2 | Secondary end point(s) |
-Complete response in delayed phase after T0
-Proportion of patiens showing CR during overall period
Other secondary efficacy endpoints to be determined for each period (Acute, Delayed, and Overall) during first cycle are:
•Proportion of patients without vomiting
•Proportion of patients without emetic episodes
•Proportion of patients without antiemetic rescue medication
•Proportion of patients without nausea (patients aged ≥ 6 years)
•Time to first vomiting
•Time to first emetic episode
•Time to first administration of rescue medication
•Time to treatment failure (time to first emetic episode or time to first administration of rescue medication, whichever occurs first).
For the subsequent cycles the following secondary endpoints are defined for each period (Acute, Delayed, and Overall):
•Proportion of patients showing CR
•Proportion of patients without vomiting
•Proportion of patients without emetic episodes
•Proportion of patients without antiemetic rescue medication
•Proportion of patients without nausea (patients aged ≥ 6 years)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
>24 to 120 hours (delayed phase) during the first cycle
0 to 120 hours (overall period) during the first cycle |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Chile |
Peru |
Russian Federation |
Serbia |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |