E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately emetogenic chemotherapy induced nausea and vomiting |
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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 |
The primary objective is to compare the effect of single doses of palonosetron 0.25mg, 0.50mg and 0.75mg administered orally versus a single intravenous dose of palonosetron 0.25mg on complete response (defined as no emetic episode and no rescue medication) during 0-24 hours and 24-120 hours after the start of moderately emetogenic chemotherapy administration. |
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E.2.2 | Secondary objectives of the trial |
Complete response daily for the 24-120 hour interval, for cumulative time periods (except for 24-120 hours) and for the overall 0-120 hour interval (Days 1 5) Complete control (defined as complete response and no more than mild nausea) daily and cumulative for the 0-120 hour interval, for the overall 0-120 hour interval (Days 1-5) and for the 24-120 hour period Number of emetic episodes daily for the 0-120 hour interval and for the overall 0-120 hour interval (Days 1-5) Time to first emetic episode Time to first administration of rescue therapy Time to treatment failure (time to first emetic episode or to administration of rescue therapy, whichever will occur first)
Further secondary efficacy objectives are included in the protocol
Adverse events Vital signs Physical examination 12-lead ECG Clinical laboratory parameters |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female, >/= 18 years of age
2. Histologically or cytologically confirmed malignant disease
3. Naïve or non-naïve to cancer chemotherapy (see Protocol Section 3.1 for definition)
4. If a patient is non-naïve, he/she must have experienced no more than mild nausea and no vomiting following any previous chemotherapy cycle.
5. A Karnofsky index of >/= 50%
6. Scheduled to receive a single intravenous dose of at least one of the following agents administered on Day 1: • any dose of oxaliplatin, carboplatin, epirubicin, idarubicin, doxorubicin, ifosfamide, irinotecan or daunorubicin or • cyclophosphamide <1500 mg/m2 or cytarabine >1g/m2.
7. Patient scheduled to receive the most emetogenic chemotherapeutic agent during a maximum of 4 hours
8. Written informed consent (with additional legal representative’s or parent’s consent if required).
9. If a patient has known hepatic, renal or cardiovascular impairment and is scheduled to receive the above mentioned chemotherapeutic agents, he/she may be enrolled in this study at the discretion of the Investigator
10. If a patient has a known history or predisposition to cardiac conduction interval abnormalities, including QTc, he/she may be enrolled in the study at the discretion of the Investigator
11. If a patient is female of childbearing potential, she must be using reliable contraceptive measures with a negative pregnancy test at the pretreatment (screening) visit |
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E.4 | Principal exclusion criteria |
1. Inability to understand or cooperate with the study procedures
2. Any investigational drugs within 30 days before the start of study treatment
3. Any drug with potential anti-emetic efficacy within 24 hours of the start of study treatment. Examples of these drugs are: 5 HT3 receptor antagonists, aprepitant, metoclopramide, phenothiazine anti-emetics (such as prochlorperazine, thiethylperazine and perphenazine), scopolamine, diphenhydramine, chlorpheniramine maleate, trimethobenzamide, all benzodiazepines except triazolam or zolpidem used once nightly for sleep, haloperidol, droperidol, tetrahydrocannabinol, or nabilone, any corticosteroid such as dexamethasone, hydrocortisone, methylprednisolone, and prednisone. Patients taking topical or inhaled steroids may be enrolled in the study.
4. Any antacid medication within 24 hours of the start of study treatment
5. Any vomiting, retching, or NCI Common Toxicity Criteria grade 2 or 3 nausea in the 24 hours preceding chemotherapy
6. Treatment with US, EU or Mexican commercially available IV palonosetron 0.25 mg (Aloxi®; Onicit®) within two weeks prior to the start of study treatment.
7. Enrollment in a previous study with palonosetron
8. Ongoing vomiting from any organic etiology
9. Presence of a clinically unstable seizure disorder with seizure activity requiring anticonvulsant medication (prophylactic anticonvulsant medication for patients free of seizure activity is allowed)
10. Any moderately or highly emetogenic chemotherapy or radiotherapy received within 1 week prior to the start of the study treatment
11. Scheduled to receive: • orally or intravenously: any dose of cisplatin, dacarbazine, streptozotocin, carmustine, mechlorethamine, hexamethylmelamine or procarbazine; or cyclophosphamide >/= 1500 mg/m2 during Days 1 to 5 of the study. See also Appendix F. • radiotherapy of upper abdomen or cranium or total body irradiation during Days 1 to 5 of the study. • Docetaxel, Paclitaxel or Pemetrexed on Day 1 in association with corticosteroids for the prevention of hypersensitivity reactions. • any low-level emetogenic chemotherapeutic agent during Days 2 to 5, if this chemotherapy, in the investigators’ opinion, requires co-administration of antiemetics. Administration of low-level emetogenic chemotherapy without antiemetics is allowed on Days 2 to 5 (see also Appendix F).
12. Known contraindication to 5-HT3 receptor antagonists |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter in this study is the proportion of patients considered to have achieved a complete response (CR) (defined as no emetic episode and no rescue medication) during the first 24 hours after the start of the first emetogenic chemotherapeutic agent administration.
The primary efficacy hypothesis is that at least one dose of oral palonosetron is not inferior to the IV dose of palonosetron (0.25mg) using a maximum delta of 15%, considering the complete response rate at 24 hours. The corresponding statistical null hypothesis is that none of the three oral palonosetron doses is non-inferior to the IV dose of palonosetron (0.25mg) using a maximum delta of 15% for complete patient response at 24 hours. |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Aloxi (0.25mg palonosetron, intravenous) and Dexamethasone (8mg, intravenous) |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |