E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
nausea and vomiting in cancer patients receiving highly emetogenic therapy |
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E.1.1.1 | Medical condition in easily understood language |
nausea and vomiting in cancer patients receiving chemotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036899 |
E.1.2 | Term | Prophylaxis against chemotherapy induced vomiting |
E.1.2 | System Organ Class | 100000004865 |
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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 demonstrate the non-inferiority of a single intravenous dose of palonosetron 0.25 mg administered as a 30-minute infusion with oral dexamethasone versus a single intravenous dose of palonosetron 0.25 mg administered as a 30-second bolus with oral dexamethasone, in terms of proportion of patients with complete response in the acute phase (0-24 hours after start of reference HEC) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of a single intravenous dose of palonosetron 0.25 mg administered as a 30-minute infusion with oral dexamethasone for the prevention of chemotherapy induced nausea and vomiting. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed written informed consent.
2. Male or female patient ≥ 18 years of age.
3. Histologically or cytologically confirmed solid tumor malignancy.
4. Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.
5. Scheduled to receive first course of one of the following reference HEC, alone or in combination with other chemotherapeutic agents* on Day 1:
- cisplatin administered as a single IV dose of ≥ 70 mg/m2
- cyclophosphamide ≥ 1500 mg/m2
- carmustine (BCNU) > 250mg/m2
- dacarbazine (DTIC)
- mechloretamine (nitrogen mustard)
The administration of the reference HEC should not extend beyond 4 hours on study Day 1.
* on Day 1, additional chemotherapeutic agents have to be administered after the start of the reference HEC administration and their administration must be completed no more than 6 hours after the start of reference HEC infusion. Low, minimally or not emetogenic chemotherapies can be administered at any time from Day 2 onwards.
6. ECOG Performance Status of 0, 1, or 2.
7. Non-childbearing female patient or female patient of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test.
8. Hematologic and metabolic status adequate for receiving a HEC regimen and fulfillment of the following criteria:
a) Total Neutrophils ≥ 1500/mm3 (Standard units: ≥ 1.5 x 10^9/L)
b) Platelets ≥ 100,000/mm3 (Standard units: ≥ 100.0 x 10^9/L)
c) Bilirubin ≤ 1.5 x Upper Limit of Normal (ULN)
d) Liver enzymes:
i. Without known liver metastases, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN
ii. With known liver metastases, AST and ALT ≤ 5.0 x ULN
e) Serum Creatinine ≤ 1.5 mg/dL (Standard units: ≤ 132.6 μMOL/L) or Creatinine Clearance ≥ 60 mL/min.
9. If a patient has a known hepatic or renal impairment, he/she may be enrolled in this study at the discretion of the Investigator, provided the inclusion criterion #8 items d) and e) are satisfied.
10. 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.
11. Able to read, understand, follow the study procedure and complete the patient diary.
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E.4 | Principal exclusion criteria |
1. Lactating woman.
2. Current use of illicit drugs or current evidence of alcohol abuse.
3. Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day 5.
4. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of reference HEC administration on Day 1 or between Days 1 to 5.
5. Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of reference HEC administration on Day 1.
6. Symptomatic primary or metastatic CNS malignancy.
7. Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any illness or medical conditions (other than malignancy) that, in the opinion of the Investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting [CINV]) or pose unwarranted risks in administering the study drugs to the patient.
8. Known hypersensitivity or contraindication to 5-HT3 receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron) or dexamethasone.
9. Known contraindication to the IV administration of 50 mL 5% glucose solution.
10. Participation in a previous clinical trial involving palonosetron.
11. Any investigational drugs (other than those given in this study) taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug during the present study.
12. Systemic corticosteroid therapy at any dose within 72hours prior to the start of reference HEC administration on Day 1. However, topical and inhaled corticosteroids are permitted.
13. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
14. Any medication with known or potential antiemetic activity within 24 hours prior to the start of reference HEC administration on Day 1, including:
• 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron)
• NK-1 receptor antagonists (e.g., aprepitant or any other new drug of this class)
• benzamides (e.g., metoclopramide, alizapride)
• phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine)
• benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to Day 1).
• butyrophenones (e.g., haloperidol, droperidol)
• anticholinergics (e.g., scopolamine, with the exception of inhaled anticholinergics for respiratory disorders, e.g., ipratropium bromide)
• antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine, chlorpheniramine)
• domperidone
• mirtazapine
• olanzapine
• prescribed cannabinoides (e.g., tetrahydrocannabinol or nabilone)
• Over The Counter (OTC) antiemetics, OTC cold or OTC allergy medications.
15. Concurrent medical condition that would preclude administration of dexamethasone for 4 days such as systemic fungal infection or uncontrolled diabetes.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with Complete Response (CR) (defined as no emetic episodes and no rescue medication) in the acute phase. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Acute phase (time interval 0 to 24 hours after the start of reference HEC) |
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E.5.2 | Secondary end point(s) |
Efficacy:
• the proportion of patients with CR during the delayed and overall phases;
• the proportion of patients with no emetic episodes during the acute, delayed and overall phases;
• the proportion of patients with no rescue medication during the acute, delayed and overall phases.
Safety:
The following safety assessments will be obtained: physical examination (PE), vital signs, 12-lead electrocardiogram (ECG), laboratory tests (hematology, blood chemistry, urinalysis), and adverse events (AEs) assessment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Acute phase (time interval 0 to 24 hours after the start of reference HEC), delayed phase (>24 to 120 hours after the start of reference HEC) and overall phase (0 to 120 hours after the start of reference HEC). |
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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 | Yes |
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 | 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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Belarus |
Bosnia and Herzegovina |
Bulgaria |
Georgia |
Greece |
Hungary |
Lithuania |
Romania |
Russian Federation |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 16 |