| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| chemotherapy induced nausea and vomiting |
|
| E.1.1.1 | Medical condition in easily understood language |
| prevention of chemotherapy induced nausea and vomiting |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
| MedDRA Classification |
| 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). |
|
| 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). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is female or male, and at least 18 years old.
2. Subject has a histologically or cytologically confirmed malignant disease.
3. Subject agrees to participate in the study by giving written informed consent. The subject may also provide consent for Future Biomedical Research however, the subject may participate in the main trial without participating in the optional Future Biomedical Research.
4. Subject is naïve (i.e., never been exposed) to MEC or HEC as defined in the Hesketh classification of emetogenic chemotherapy agents (Appendix 6.2).
5. The subject will receive a single IV dose of one or more MEC agents (that when combined would be classified as a MEC agent regimen in accordance with current multiple agent emetogenicity classification guidelines based on the Hesketh scale – see Appendix 6.2) on Treatment Day 1. Combinations of an anthracycline and cyclophosphamide (AC MEC) are not permitted.
--concomitant radiotherapy of the extremities, breast and chest, as well as other chemotherapy agents that are categorized as having “low” or “minimal” emetic risk per the Hesketh classification of emetogenic chemotherapy agents
may be added to the above chemotherapy regimens on Day 1.
--Chemotherapy agents classified as “minimal” emetic risk may be used throughout the treatment period.
--Subjects requiring cyclical regimens may be enrolled in the trial as long as the chemotherapy or chemo-radiotherapy regimen is an otherwise permitted MEC regimen and the first dose of the subsequent cycle does not occur until after
completion of all protocol-specified Treatment Period Day 6 assessments.
--Multiday use of MEC or LEC through Day 3 is permitted, when the continuation of the MEC or LEC is part of the overall Day 1 MEC regimen.
These multiday regimens will be limited to approximately 15% of the total
enrollment. Note that multiple agent MEC regimens in which a LEC starts on
Day 1 and continues uninterrupted into Day 2 will not be considered part of the 15% limit for multiday regimens.
--Oxaliplatin will be limited to approximately 30% of the total enrollment.
6. Subject has a predicted life expectancy at least 4 months
7. Subject has a Karnofsky score 6.3).
8. A female of reproductive potential must demonstrate a negative urine pregnancy test at the pre-study visit and on Day 1 prior to receiving study medication. If the urine pregnancy test is positive, the subject can be enrolled only if a subsequent serum pregnancy test obtained during screening is negative. The subject must also agree to remain abstinent or use medically acceptable
contraception for at least 14 days prior to, throughout, and for at least 1 month following the last dose of study medication or longer depending on local country requirements. Subjects using hormonal contraception must agree to add a barrier
form of contraception because aprepitant decreases the plasma concentration of ethinyl-estradiol by an undefined mechanism, which may reduce the efficacy of contraceptives containing these agents. NOTE: Barrier methods of contraception create a physical barrier between sperm and egg cells to prevent fertilization (e.g., condoms, diaphragm, cervical cap,
intrauterine device and contraceptive sponge).
Examples of acceptable methods of birth control are provided below:
Condom in combination with a spermicide (e.g., foam, gel, film, cream,
suppository).
Medically prescribed occlusive cap (diaphragm or cervical cap) with
spermicide.
Medically prescribed intrauterine device (IUD) with a spermicide.
Hormonal contraceptives prescribed by a physician (oral combined,
hormonal vaginal ring, hormonal implant or depot-injectable) plus any of the
above barrier forms of birth control.
Sexual relations with a male partner who has had a vasectomy at least 3
months prior to the screening visit.
Sexual abstinence: Females who are able to become pregnant but are not
currently sexually active must agree to use medically acceptable birth control
if they become sexually active during the course of the study. In regions
where abstinence is not considered an acceptable form of birth control, the
subject must agree to use another acceptable form of birth control.
A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subject who is not of reproductive potential is defined as one who has either:
reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the
local laboratory, or 12 months of spontaneous amenorrhea); or bilateral tubal ligation; or
six weeks post-surgical bilateral oophorectomy with or without hysterectomy
9. Subject is able to read, understand, and complete study diary and questionnaire. |
|
| E.4 | Principal exclusion criteria |
1. Subject has vomited in the 24 hours prior to treatment Day 1.
2. Subject has a symptomatic primary or metastatic symptomatic CNS malignancy causing nausea and/or vomiting. Subject who is asymptomatic is allowed to participate at the judgment of the investigator.
3. Subject 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. Subject has received or is scheduled to receive total body irradiation (TBI) or radiation therapy to the abdomen (includes the level of the diaphragm and below), pelvis, head and neck within 1 week prior to, or during Days 1 through 6 of the
Treatment Period. NOTE: Subjects may receive concomitant radiotherapy or radiation sensitization
of the extremities, breast or chest on Day 1, only if a non-AC MEC is also being administered to treat the primary cancer diagnosis.
5. Subject has an active infection (e.g., pneumonia), any uncontrolled disease (e.g.,
diabetic ketoacidosis, congestive heart failure, bradyarrhythmias, 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 subject.
6. Subject has a known history of QT prolongation.
NOTE: The subject’s ECG obtained during screening, within 7 days prior to the
planned initiation of study medication, must be reviewed and found clinically acceptable in the judgment of the investigator, prior to calling the
IVRS for subject treatment assignment.
7. Subject 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. Subject is mentally incapacitated or has a significant emotional or psychiatric
disorder that, in the opinion of the investigator, precludes study entry.
9. Subject has a history of hypersensitivity to aprepitant, ondansetron, or
dexamethasone (See Section 7. Attachments).
10. Subject is pregnant or breast-feeding. (Subjects of reproductive potential are
required to have a negative urine pregnancy test prior to entering the study; see inclusion criterion #8).
11. Subject has participated in a study with aprepitant or has taken a non-approved
(investigational) drug within the last 4 weeks.
12. Subject is currently taking warfarin or other CYP2C9 substrates.
13. Other Excluded Medications:detailed on page 33of protocol.
17. Subject has used benzodiazepines or opiates, except for single daily doses of triazolam, temazepam or midazolam, in the 48 hours prior to Treatment Day 1. Continuation of chronic benzodiazepines or opiate therapy is permitted
provided it was initiated at least 48 hours prior to Treatment Day 1.
18. Subject has a concurrent medical condition that would preclude administration of
dexamethasone such as a systemic fungal infection or uncontrolled diabetes.
19. Subject is taking systemic corticosteroid therapy at any dose; however, topical and
inhaled corticosteroids are permitted.
NOTE: Subjects receiving taxanes or pemetrexed as part of their chemotherapeutic regimen should receive dexamethasone premedication as
described in Appendix 6.6 (paclitaxel), Appendix 6.7 (docetaxel) and Appendix 6.8 (pemetrexed). In lieu of Bottles B and C these subjects will
receive “open –label” dexamethasone which will be sourced locally (provided by the investigator or authorized designee) where available, or supplied by the SPONSOR if not available locally.
Laboratory Results:
20. Subject has a positive serum pregnancy test.
21. Subject has abnormal laboratory values. Subjects are not eligible if their laboratory
values meet any of the following criteria:
21.1 Absolute Neutrophil Count <1500/mm3 and WBC count <3000/mm3
21.2 Platelet Count <100,000/mm3
21.3 AST (aspartate transaminase) >2.5 x upper limit of normal
21.4 ALT (alanine transaminase) >2.5 x upper limit of normal
21.5 Bilirubin >1.5 x upper limit of normal
21.6 Creatinine >1.5 x upper limit of normal
NOTE: All laboratory results, completed within 7 days of initiation of study
medication, must be reviewed and found clinically acceptable in the judgment of
the investigator prior to calling IVRS for subject treatment assignment.
Laboratory retesting is permitted during the Screening period if deemed clinically
appropriate by the investigator. See Appendix 6.4 for a full list of laboratory tests. |
|
| 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.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 25 to 120 hours following initiation of chemotherapy |
|
| 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). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 0 to 120 hours following initiation of chemotherapy |
|
| 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 | 2 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 |
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