E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric Chemotherapy induced nausea and vomiting (CINV) |
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E.1.1.1 | Medical condition in easily understood language |
Nausea and vomiting due to chemotherapy |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
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 | 10052401 |
E.1.2 | Term | Vomiting post chemotherapy |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 | 10056989 |
E.1.2 | Term | Nausea post chemotherapy |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 compare the three-day oral aprepitant regimen (aprepitant plus ondansetron), to ondansetron alone with respect to the efficacy endpoint of Complete Response (no vomiting and no use of rescue medication) in the 120 hours following initiation of emetogenic chemotherapy in Cycle 1 (overall phase).
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E.2.2 | Secondary objectives of the trial |
Efficacy:
(1) To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of Complete Response in the 0 to 24 hours following the initiation of emetogenic chemotherapy in Cycle 1 (acute phase).
(2) To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of Complete Response in the 25 to 120 hours following the initiation of emetogenic chemotherapy in Cycle 1 (delayed phase).
(3) To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of No Vomiting, regardless of rescue medication use, in the 120 hours following the initiation of emetogenic chemotherapy in Cycle 1 (overall phase).
Safety:
To assess the safety and tolerability of the three-day oral aprepitant regimen in patients from birth to 17 years of age who are receiving emetogenic chemotherapy in Cycle 1.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is 0 (at least 37 weeks gestation and ≥ 3kg) to 17 years of age at time of study entry.
2. Parent/guardian (legally authorized representative) agrees to the patient's participation as indicated by parent/legal guardian signature on the informed consent form. Patients 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 questionnaires, and is willing to keep scheduled study visits.
3. Patient is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of emetogenicity for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting.
4. Patient is expected to receive ondansetron as part of their antiemetic regimen.
5. 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.
6. Patient aged >10 years has a Karnofsky score ≥ 60; patient aged ≤ 10 years has a Lansky Play Performance score ≥ 60 (Appendix 6.2).
7. Patient has a predicted life expectancy of ≥ 3 months.
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E.4 | Principal exclusion criteria |
1. Patient has vomited in the 24 hours prior to Treatment Day 1.
2. Patient is allergic to aprepitant, ondansetron, or any other 5-HT3 antagonist.
3. Patient has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting. Patient who is asymptomatic is allowed to participate.
4. Patient has abnormal laboratory values as follows (deviations from these guidelines require discussion with the Merck Clinical Monitor):
a. Bone Marrow Function
I. Peripheral absolute neutrophil count (ANC) <1000/mm3
II. Platelet count <100,000/ mm3
b. Liver Function
I. AST>5.0 x upper limit of normal (ULN) for age
II. ALT>5.0 x upper limit of normal (ULN) for age
III. Bilirubin > 1.5 x upper limit of normal (ULN) for age
c. Renal function
I. A serum creatinine > 1.5 x upper limit of normal (ULN) for age
5. 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.
6. 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 < the equivalent of 20 mg of prednisone.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of patients with Complete Response (No Vomiting and no use of rescue medication) in the 120 hours following initiation of emetogenic chemotherapy.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
120 hours following initiation of emetogenic chemotherapy |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints will be (1) the proportion of patients with Complete Response in the 0 to 24 hours following initiation of emetogenic chemotherapy; (2) the proportion of patients with Complete Response in the 25 to 120 hours following initiation of emetogenic chemotherapy; and (3) the proportion of patients with No Vomiting, irrespective of use of rescue medication, in the 120 hours following initiation of emetogenic chemotherapy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The proportions of patients with Complete Response and No Vomiting will be summarized at 3 time periods; 0 to 24 (acute), 25 to 120 (delayed), and 0 to 120 (overall) hours post initiation of emetogenic chemotherapy, with 0 to 120 hours the primary time point. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | 2 |
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 | 28 |
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 |
Croatia |
Denmark |
Dominican Republic |
Ecuador |
France |
Greece |
Guatemala |
Hungary |
Israel |
Italy |
Korea, Republic of |
Lithuania |
Mexico |
Netherlands |
Panama |
Peru |
Poland |
Portugal |
Russian Federation |
Slovenia |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |