E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy-induced nausea and vomiting (CINV) associated with emetogenic chemotherapy. |
Nausea e vomito (CINV) indotti da chemioterapia associata a chemioterapia emetogena. |
|
E.1.1.1 | Medical condition in easily understood language |
Nausea and vomiting caused by chemotherapy. |
Nausea e vomito indotti da chemioterapia. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 100000004865 |
|
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 determine the appropriate dosing regimen of fosaprepitant for the
prevention of CINV in pediatric patients birth to 17 years of age, by assessing the pharmacokinetic and pharmacodynamic parameters, and the safety and tolerability of the administered dose of fosaprepitant, concomitantly with IV ondansetron, in patients from birth to 17 years of age receiving emetogenic chemotherapy (very highly emetogenic
chemotherapy [VHEC], highly emetogenic chemotherapy [HEC], or moderately emetogenic chemotherapy [MEC]), or a chemotherapy regimen not previously tolerated due to vomiting, for a documented malignancy. |
xxxxx |
|
E.2.2 | Secondary objectives of the trial |
The efficacy, with respect to Complete Response and No Vomiting, of the
fosaprepitant regimen when administered concomitantly with ondansetron, with or without dexamethasone, will be explored in pediatric patients birth to 17 years of age receiving emetogenic chemotherapy (VHEC, HEC, or MEC), or a chemotherapy regimen not previously tolerated due to vomiting, for a documented malignancy. |
xxxxx |
|
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 |
OTHER SUBSTUDIES: FBR on samples collected using swabs.
Explore and identify biomarkers to understand the pathology and/or therapeutic treatments.
|
ALTRI SOTTOSTUDI: Ricerca Biomedica Futura su campioni prelevati utilizzando tamponi boccali.
Obiettivo è esplorare e identificare biomarcatori per conoscere meglio la patologia e/o i trattamenti terapeutici.
|
|
E.3 | Principal inclusion criteria |
- Patient is 0 (at least 37 weeks gestation) to 17 years of age at time of
study entry (randomization).
- Parent/guardian (legally authorized representative) agrees to the patient's participation as indicated by parent/legal guardian signature on the informed consent form. Patient 12 to 17 years of age, or as required by local regulation, assents and has the ability to understand the nature and intent of the study including the ability to comply with study procedures, complete study diary, and is willing to keep scheduled study visits. The parent/guardian or patient may also provide consent/assent for Future Biomedical Research. However, the patient may participate in the main trial without participating in the Future Biomedical Research.
- Patient is scheduled to receive chemotherapeutic agent(s) associated
with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting.
- Female patient who has begun menses has a negative urine pregnancy test prior to randomization. A female patient who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication. Women taking
oral contraception must agree to add a barrier form of contraception.
For countries where abstinence is not considered an acceptable method of birth control, a locally acceptable birth control method must be used.
- Patient has a preexisting functioning central venous catheter available for study drug administration.
- Patient's weight should not be less than the 3rd percentile for age and
gender (and no less than 3.0 kg) per investigator judgment using available local growth chart(s). |
xxxxx |
|
E.4 | Principal exclusion criteria |
- Patient has vomited in the 24 hours prior to chemotherapy initiation on
Treatment Day 1.
- Patient is currently a user of any illicit drugs (including marijuana) or
has current evidence of alcohol abuse (defined using the Diagnostic and
Statistical Manual-IV [DSM-IV] criteria) as determined by the investigator.
- Patient has received or will receive radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the course of the study.
- Patient is allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist.
- Patient has an active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or a history of any illness which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in
administering study drug or concomitant therapy to the patient.
- Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes
study entry.
- Patient has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation.
- Patient has had benzodiazepine or opioid therapy initiated within 48
hours of study drug administration, except for single daily doses of
triazolam, temazepam, or midazolam.
* Continuation of chronic benzodiazepine or opioid therapy is permitted provided it was initiated at least 48 hours prior to study drug administration.
- Patient has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen.
Exceptions:
• Patients who are receiving chronic (>72 hours), daily steroid therapy
can be enrolled provided the steroid dose is not >0.14 mg/kg (up to 10 mg) of prednisone daily or equivalent.
• For supportive care, patients are permitted to receive a single dose of corticosteroid within 3 days prior (but not on the day of study drug administration) provided it is less than the equivalent of 20 mg of prednisone.
- Patient is currently taking warfarin.
- Patient has ever participated in a study of aprepitant or fosaprepitant,
or has taken a non-approved (investigational) drug within the last 4
weeks. Note: Patients in investigational studies with marketed chemotherapeutic agents (whether explicitly for children or only marketed for adults and usually administered to children with the appropriate dose adjustments) are allowed to enroll if they fulfill all
other entry criteria. |
xxxxx |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Pharmacokinetic (PK) Endpoints: Cmax, Tmax, AUC0-infinity, t1/2, CL/F estimated by population methods, including the use of historic data
in population modeling, in each age group for the 3 fosaprepitant treatment groups in Cycle 1.
- Safety Endpoints: Clinical and laboratory adverse events that are
considered drug-related, serious, serious drug-related, or lead to
discontinuation of study therapy. |
xxxxx |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For PK: Five scheduled time points for PK sampling
1. End of the fosaprepitant infusion
2. 2 to 4 hours after (completion of) fosaprepitant dosing
3. 5 to 7 hours after fosaprepitant dosing
4. 8 to 10 hours after fosaprepitant dosing
5. 23 to 25 hours after fosaprepitant dosing
For Safety: Throughout the study (Screening, Treatment, Post-Treatment, and/or Follow-Up/DC). |
Per PK: 5 punti per il campionamento PK:
1. Fine dell'infusione di fosaprepitant;
2. da 2 a 4 ore dopo il completamento del dosaggio del fosaprepitant;
3. da 5 a 7 ore dopo la somministrazione del fosaprepitant;
4. da 8 a 10 ore dopo la somministrazione del fosaprepitant;
5. da 23 a 25 ore dopo la somministrazione del fosaprepitant.
Per la sicurezza: in tutto lo studio (screening, trattamento, post-trattamento, Follow-Up/DC). |
|
E.5.2 | Secondary end point(s) |
- Pharmacodynamic (PD) Endpoints: The proportion of patients with Complete Response (CR) in the 25 to 120 hours after initiation of chemotherapy (delayed phase). Other PD endpoints will be the proportion of patients with CR in the 0 to 24 hours after chemotherapy
(acute phase); and the proportion of patients with CR in the 0 to 120
hours after chemotherapy (overall phase); and also, the proportion of
patients with No Vomiting. Irrespective of use of rescue medication, in the overall, acute, and delayed phases. |
xxxxx |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For PD: Over the first 120 hours (to Day 6) following the initiation of chemotherapy (Tzero). |
Per PD: durante le prime 120 ore (al 6° giorno) dopo l'avvio della chemioterapia (Tzero). |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
parzialmente in cieco |
partial blind |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Brazil |
Canada |
Chile |
Colombia |
India |
Mexico |
Peru |
Russian Federation |
South Africa |
Turkey |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 23 |
E.8.9.2 | In all countries concerned by the trial days | 0 |