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 main objective of this study is to assess the safety of single oral doses of palonosetron 0.75 mg (with or without concomitant corticosteroids) used for the prevention of moderately emetogenic chemotherapy induced nausea and vomiting in repeated (up to a maximum of four) and consecutive chemotherapeutic cycles. |
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E.2.2 | Secondary objectives of the trial |
As a secondary objective, the continued efficacy of a single oral dose of palonosetron 0.75 mg (with or without corticosteroids) will be assessed in up to a maximum of four consecutive moderately emetogenic chemotherapy cycles for the prevention of moderately emetogenic chemotherapy induced nausea and vomiting. |
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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. Patient scheduled to receive repeated and consecutive moderately emetogenic chemotherapy cycles employing the same basic moderately emetogenic regimen (single or multi-drug regimen). This can include changes in dose or discontinuation of concomitant chemotherapeutic agents as clinically appropriate, as long as the agent that defines the regimen as moderately emetogenic is still included and no highly emetogenic agents are added.
4. Naïve or non-naïve to cancer chemotherapy (see Section 3.1 for definition)
5. If a patient is non-naïve before the first study cycle, he/she must have experienced no more than mild nausea and no vomiting following any previous chemotherapy cycle
6. A Karnofsky index of >/= 50%
7. Scheduled to receive a single intravenous dose of at least one of the following moderately emetogenic 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
8. Patient scheduled to receive the most emetogenic chemotherapeutic agent during a maximum of 4 hours
9. Written informed consent (with additional legal representative’s or parent’s consent if required)
10. If a patient has a 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.
11. If a patient has a known history or predisposition to cardiac conduction interval abnormalities, including QTc, he/she may be enrolled in this study at the discretion of the Investigator.
12. If a patient is female of childbearing potential, she must be using reliable contraceptive measures with a negative pregnancy test before any study treatment administration.
13. The time interval between two consecutive study drug administrations (between the two ‘Day 1’ days in two consecutive study cycles) must be at least seven days (i.e. study drug can be administered at weekly intervals). |
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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 study entry
3. Any drug with potential anti-emetic efficacy within 24 hours of the intake 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 intake 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 intake 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. Palonosetron 0.75 mg not administered in consecutive chemotherapy cycles, i.e. if a chemotherapy cycle is performed without oral palonosetron 0.75 mg administration after the patient has already received at least one preceding cycle in this study (including palonosetron 0.75 mg), the patient has to be excluded from further participation in the study.
11. Scheduled to receive: • Moderately emetogenic chemotherapy within 7 days prior to the study, on Days 2-5 of each study cycle, or on any day between two consecutive cycles • Orally or intravenously: any dose of cisplatin, dacarbazine, streptozotocin, carmustine, mechlorethamine, hexamethylmelamine or procarbazine; or cyclophosphamide >/= 1500 mg/m2 within 7 days prior to the study or during the study (see also Appendix E) • Radiotherapy of upper abdomen or cranium or total body irradiation within 7 days prior to the study or during 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 of each study cycle, 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 E).
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 objective of the study is the safety assessment, which will be analyzed in a descriptive way through the following parameters:
• Adverse events (collected from patients during visits or from vital signs, physical examination, ECG or clinical laboratory parameters) • Vital signs (blood pressure, heart rate) • Physical examination (covering twelve body systems) • 12-lead ECG • Clinical laboratory parameters (hematology, blood chemistry, urinalysis)
The parameters of main interest for efficacy are Complete Response (CR), defined as no emetic episode and no rescue medication, during the first 24 hours (CR0-24h) and during the period from 24 hours to 120 hours (CR24-120h) after the administration of the first emetogenic chemotherapeutic agent, at each study cycle. |
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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 | 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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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
| |
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 | 12 |
E.8.9.1 | In the Member State concerned days | |
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 | 12 |