| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| chemotherapy induced nausea and vomiting |
| Náuseas y los vómitos asociados a la quimioterapia |
|
| E.1.1.1 | Medical condition in easily understood language |
| prevention of chemotherapy induced nausea and vomiting |
| Prevención de las náuseas y los vómitos asociados a la quimioterapia |
|
| 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 | 14.1 |
| 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 |
|
| 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 | 10056989 |
| E.1.2 | Term | Nausea post chemotherapy |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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 single-dose fosaprepitant 150 mg regimen to the control regimen in terms of the proportion of patients with Complete Response (no vomiting and no use of rescue medication) from 25 to 120 hours (delayed phase) following initiation of moderately emetogenic chemotherapy (MEC). |
| Comparar el tratamiento con una dosis única de 150 mg de fosaprepitant con el tratamiento de control en cuanto a la proporción de pacientes con respuesta completa (ausencia de vómitos y de uso de medicación de rescate) de 25 a 120 horas (fase tardía) después del inicio de la quimioterapia moderadamente emetógena (QME). |
|
| E.2.2 | Secondary objectives of the trial |
| To compare the single-dose fosaprepitant 150 mg regimen and the control regimen in terms of the proportion of patients with a Complete Response (no vomiting and no use of rescue medication) in the overall phase (in the 120 hours following initiation of MEC). |
| Comparar el tratamiento con una dosis única de 150 mg de fosaprepitant con el tratamiento de control en cuanto a la proporción de pacientes con respuesta completa (ausencia de vómitos y de tratamiento de rescate) en la fase total (en las 120 horas siguientes al inicio de la QME). |
|
| 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 |
| A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of a Single 150 mg Dose of Intravenous Fosaprepitant Dimeglumine for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Moderately Emetogenic Chemotherapy |
Estudio en fase III, aleatorizado, doble ciego, controlado con un comparador activo y de grupos paralelos, realizado en condiciones de enmascaramiento interno, para examinar la eficacia y la seguridad de una dosis única de 150 mg de dimeglumina de fosaprepitant por vía intravenosa para la prevención de las náuseas y los vómitos inducidos por la quimioterapia (NAVIQ) moderadamente emetógena.
La muestra de ADN obtenida en este ensayo se utilizará para estudiar diversas causas genéticas de las respuestas de los sujetos a un fármaco |
|
| E.3 | Principal inclusion criteria |
1.Patient is female or male, and is ?18 years of age.
2.Patient has a histologically or cytologically confirmed malignant disease.
3.Patient agrees to participate in the study by giving written informed consent. The patient may also provide consent for Future Biomedical Research. However, the patient may participate in the main trial without participating in Future Biomedical Research.
4. Patient is naïve to moderately and highly emetogenic chemotherapy as defined in the Hesketh classification of emetogenic chemotherapy agents (Appendix 6.2).
5. Scheduled to receive a single IV dose of one or more MEC agents except for the combination of anthracycline and cyclophosphamide (AC MEC) such as: Alemtuzumab, Daunorubicin,Azcitidine, Doxorubicin, Bendamustine, Epirubicin, Carboplatin, Idarubicin, Clofarabine, Ifosfamide,
Cyclophosphamide(<1500mg/m2) Irinotecan, Cytarabine (>1 g/m2), Oxaliplatin
6. Patient has a predicted life expectancy ?4 months.
7. Patient has a Karnofsky score ?60 (see Appendix 6.3).
8. A female of reproductive potential must demonstrate a negative urine pregnancy test at the prestudy visit to meet eligibility and agree to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least 1 month following the last dose of study medication
9. Patient is able to read, understand, and complete study diary and questionnaire. |
1. Varones y mujeres de 18 años de edad en adelante.
2. El paciente presenta una enfermedad maligna confirmada por histología o citología.
3. El paciente acepta participar en el estudio firmando el consentimiento informado por escrito. El paciente también podrá otorgar su consentimiento para investigaciones biomédicas futuras. No obstante, el paciente podrá participar en el ensayo principal sin participar en investigaciones biomédicas futuras.
4. El paciente nunca ha recibido quimioterapia moderadamente ni sumamente emetógena, según se define en la clasificación de Hesketh de quimioterápicos emetógenos (Apéndice 6.2)
5. Está previsto que el paciente reciba una dosis única intravenosa de uno o más fármacos de quimioterapia moderadamente emetógena el día 1, excepto la combinación de una antraciclina y ciclofosfamida (QME AC): Alentuzumab, Daunorubicina, Azacitidina , Doxorubicina, Bendamustina, Epirubicina, Carboplatino, Idarubicina, Clofarabina, Ifosfamida, Ciclofosfamida (<1.500 mg/m2), Irinotecán, Citarabina (>1 g/m2), Oxaliplatino.
6. El paciente tiene una esperanza de vida prevista ? 4 meses.
7. El paciente tiene una puntuación de Karnofski ? 60 (Apéndice 6.3).
8. Las mujeres en edad fértil deberán dar negativo en una prueba de embarazo realizada en la visita de antes del estudio para poder participar y comprometerse a mantener la abstinencia sexual o usar un método anticonceptivo de barrera desde al menos 14 días antes del estudio, durante el tratamiento y durante al menos un mes después de la última dosis de la medicación del estudio.
9.El paciente es capaz de leer, comprender y rellenar el diario y los cuestionarios del estudio |
|
| E.4 | Principal exclusion criteria |
1. Patient has vomited in the 24 hours prior to treatment Day 1.
2. Patient has a symptomatic primary or metastatic symptomatic CNS malignancy causing nausea and/or vomiting. Patient who is asymptomatic is allowed to participate.
3. Patient is scheduled to receive the combination of anthracycline + cyclophosphamide or any dose of cisplatin or chemotherapy agent classified as highly emetogenic in the Hesketh classification of emetogenic chemotherapy agents (Appendix 6.2).
4. Patient has received or will receive radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 through Day 6.
5. Patient has an active infection (e.g., pneumonia), any uncontrolled disease (e.g., diabetic ketoacidosis, congestive heart failure, bradyarrythmia?s, pre-existing gastrointestinal conditions/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/comparator to the patient.
6. Patient has a known history of QT prolongation.
7. Patient currently uses any illicit drugs, including marijuana, or has current evidence of alcohol abuse (defined using DSM-IV criteria) as determined by the investigator.
8. Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
9. Patient has a history of hypersensitivity to aprepitant, ondansetron, or dexamethasone (See Section 7. Attachments).
10. Patient is pregnant or breast-feeding. (Patients of childbearing potential are required to have a negative urine pregnancy test prior to entering the study; see inclusion criterion #8).
11. Patient has participated in a study with aprepitant or has taken a non-approved (investigational) drug within the last 4 weeks.
12. Patient is currently taking warfarin or other CYP2C9 substrates.
13.? 16. Other Excluded Medications: CYP3A4 Inducers, CYP3A4 substrates, CYP3A4 Inhibitors, Antiemetics.
17. Patient has used benzodiazepines or opiates, except for single daily doses of triazolam, temazepam or midazolam, in the 48 hours prior to Treatment Day 1.
18. Patient has a concurrent medical condition that would preclude administration of dexamethasone such as a systemic fungal infection or uncontrolled diabetes.
19. Patient is taking systemic corticosteroid therapy at any dose; however, topical and inhaled corticosteroids are permitted.
20. Patient has a positive serum pregnancy test.
21. Abnormal laboratory values. |
1. El paciente ha vomitado en las 24 horas previas al día 1 de tratamiento.
2. El paciente tiene un tumor maligno sintomático, primario o metastásico, en el SNC que provoca náuseas o vómitos. Podrán participar en el estudio los pacientes asintomáticos.
3. Está previsto que el paciente reciba la combinación de una antraciclina + ciclofosfamida o cualquier dosis de cisplatino o un quimioterápico clasificado como sumamente emetógeno en la clasificación de Hesketh de quimioterápicos emetógenos (Apéndice 6.2).
4. El paciente ha recibido o va a recibir radioterapia en el abdomen o en la pelvis en la semana previa a los días de tratamiento 1 a 6.
5. El paciente sufre una infección activa (p. ej., una neumonía), alguna enfermedad no controlada (p. ej., cetoacidosis diabética, insuficiencia cardíaca congestiva, bradiarritmia, enfermedad digestiva preexistente u obstrucción digestiva) distinta del tumor maligno, o tiene antecedentes de una enfermedad que, en opinión del investigador, podría confundir los resultados del estudio o hacer que la administración del fármaco del estudio/comparador suponga un riesgo injustificado para el paciente.
6. El paciente tiene antecedentes conocidos de prolongación del QT.
7. El paciente consume actualmente algún tipo de droga, incluida la marihuana, o el investigador determina que hace un consumo excesivo de alcohol (definido por los criterios DSM IV).
8. El paciente es mentalmente incapaz o padece algún trastorno emocional o psiquiátrico importante que, en opinión del investigador, impide su participación en el estudio.
9. El paciente tiene antecedentes de hipersensibilidad al aprepitant, al ondansetrón o a la dexametasona (véase la sección 7. Anexos).
10. La paciente está embarazada o amamantando. (Las mujeres en edad fértil deberán obtener resultados negativos en una prueba de embarazo en orina realizada antes de entrar en el estudio; véase el criterio de inclusión 8.)
11. El paciente ha participado en un estudio con aprepitant o ha tomado un fármaco no aprobado (experimental) en las últimas 4 semanas.
12. El paciente recibe actualmente warfarina u otros sustratos de la CYP2C9.
13 -16 Otros medicamentos excluidos: Inductores de la CYP3A4, Sustratos de la CYP3A4, Inhibidores de la CYP3A4, Antieméticos
17. El paciente ha usado benzodiazepinas u opiáceos, excepto dosis únicas diarias de triazolam, temazepam o midazolam, en las 48 horas previas al día 1 de tratamiento |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy: The single-dose fosaprepitant 150 mg regimen provides superior control of CINV compared to the control regimen as measured by the proportion of patients with Complete Response in the delayed phase.
Safety: The single-dose fosaprepitant 150 mg regimen is well tolerated in patients receiving MEC. |
Eficacia:El tratamiento con una dosis única de 150 mg de fosaprep itant proporciona un control superior de las NAVIQ en comparación con el tratamiento de control a juzgar por la proporción de pacientes con respuesta completa en la fase tardía.
Seguridad: El tratamiento con una dosis única de 150 mg de fosaprepitant es bien tolerado por los pacientes que reciben QME. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 0 to 120 hours following initiation of chemotherapy |
| Seguimiento desde el inicio de la quimioterápia de 0 a 120 horas. |
|
| E.5.2 | Secondary end point(s) |
| The single-dose fosaprepitant 150 mg regimen is superior to the control regimen with respect to the proportion of patients with a Complete Response in the overall phase (0in the 120 hours following initiation of MEC). |
| El tratamiento con una dosis única de 150 mg de fosaprepitant es superioral tratamiento de control en cuanto a la proporción de pacientes con respuesta completa (ausencia de vómitos y de tratamiento de rescate) en la fase total (en las 120 horas siguientes al inicio de la QME). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 0 to 120 hours following initiation of chemotherapy |
| Seguimiento desde el inicio de la quimioterápia de 0 a 120 horas. |
|
| 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 | Yes |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| 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 |
| Philippines |
| Russian Federation |
| South Africa |
| Thailand |
| Turkey |
| Ukraine |
| United States |
| Venezuela, Bolivarian Republic of |
|
| 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 | 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 |
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