The study aims at investigating if a three-drug antiemetic regimen is superior in preventing nausea and vomiting in patients receiving radiotherapy and weekly chemotherapy than a two-drug regimen (standard treatment) as currently recommended in guidelines. A pilot study makes it reasonable to believe that the addition of a third drug (a neurokinin1 receptor antagonist) will increase the proportion of patients with no vomiting in the course of combined chemo-radiotherapy. MedDRA version: 14.1 Le
Conditions
Interventions
Trade Name: Aloxi
Pharmaceutical Form: Injection
INN or Proposed INN: PALONOSETRON
CAS Number: 135729-56-5
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration num
Sponsors
Odense University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has a diagnosis of cervical cancer. 2. The patient understands the nature and purpose of this study and the study procedures and has signed informed consent. 3. The patient is aged > 18 years. 4. The patient must be both chemo- and radiotherapy naïve. 5. The patient is scheduled to receive fractionated radiotherapy (at least 23 fractions) and concomitant weekly cisplatin at a dose of = 40 mg/m2 for at least five weeks, and planned brachy therapy should preferentially be scheduled after the fifth week of treatment. 6. Chemotherapy with an emetic risk potential of minimal or mild (up to 30%) is allowed on days 1-4 (see ref. 17). 7. The patient has a WHO Performance Status of = 2. 8. Hematologic and metabolic status must be adequate for receiving weekly cisplatin in a dose of = 40 mg/m2, and meet the following criteria: • Total neutrophils = 1500/mm3 (Standard units : =1.5 x 109/L) • Platelets = 100,000/mm3 (Standard units: =100.0 x 109/L) • Bilirubin = 1.5 x ULN (Upper Limits of Normal) • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2.5 x ULN • GFR = 50 ml/min 9. The patient is able to read, understand, and complete questionnaires and daily components of the Patient Diary for each study cycle. 10. For patients of childbearing potential, urine human chorionic gonadotropin (hCG) (urine dipstick pregnancy test) results must be negative at screening, and these patients must agree to one of the following methods of contraception: • Male partner who is sterile prior to the patient’s entry into the study and is the sole sexual partner for that patient. • Double-barrier method of contraception consisting of spermicide with either condom or diaphragm. • Complete abstinence from intercourse for two weeks before study entry and throughout the study period plus a period after the trial to account for elimination of the drug (minimum of eight days). Oral contraceptives (e.g., oral, injectable, trans dermal, or implantable) are NOT considered safe because of potential lowered ethinyloestradiol exposures when co-administered with fosaprepitant and dexamethasone (see Appendix 1, p230). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. The patient has a current malignant diagnosis other than cervical cancer, with exception of non-melanoma skin cancers. 2. The patient is aged = 18 years. 3. The patient is scheduled to receive less than five weeks (or 23 fractions) of fractionated radiotherapy and concomitant weekly cisplatin. 4. The patient has been previously treated with radiotherapy, and/or chemotherapy. 5. The patient has a WHO Performance Status of > 2. 6. Hematologic and metabolic status are inadequate, i.e. • Total neutrophils 1.5 x ULN • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x ULN • GFR = 50 ml/min 7. The patient is unable to read, understand, and complete the forms required for the study. 8. The patient is pregnant or lactating. 9. The patient with a reproductive potential refuses to use adequate contraception. 10. The patient has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours preceding the first dose of study medication. 11. The patient has a history active peptic ulcer disease, gastrointestinal obstruction, gastrointestinal carcinoma, increased intracranial pressure, hypercalcemia, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV/RINV) or pose an unwarranted risk to the patient. 12. The patient has a known hypersensitivity or contraindication to palonosetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of fosaprepitant. 13. The patient has previously received an NK1 receptor antagonist. 14. The patient has received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug other than the study medication during the study period. 15. The patient has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medications. Opiate drugs for cancer pain will be permitted if the patient has been on a stable dose and has not experienced emesis or clinically significant nausea from the narcotics in the 24 hours preceding the first dose of study medication. 16. The patient has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drugs. This includes, but is not limited to: • 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted within 7 days prior to receiving study drugs. • Benzamide / benzamide derivatives (e.g., metoclopramide, alizapride). • Benzodiazepines (except if the patient is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to the first dose of casopitant investigational product and study medications). • Phenothiazines (e.g., prochlorperazine, promethazine, metopimazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine). • Butyrophenone (e.g., haloperidol, droperidol). • Corticosteroids (e.g., dexamethasone, methylprednisolone, prednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders). • Anticholinergics (e.g., scopolamine). • Antihistamines (e.g., cy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare an antiemetic regimen consisting of fosaprepitant dimeglumine (Ivemend®), palonosetron (Aloxi®), and dexamethasone (active arm) and a regimen consisting of palonosetron, dexamethasone, and placebo (control arm) with respect to efficacy; the proportion of subjects with no vomiting, i.e. sustained no emesis rate - during five weeks of fractionated (5 days a week) radiotherapy and concomitant weekly cisplatin at a dose of = 40 mg/m2.;Secondary Objective: 1. To compare the fosaprepitant regimen and the control regimen in terms of the proportion of subjects with complete response in the 7 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of = 40 mg/m2. 2. To compare the fosaprepitant regimen and the control regimen in terms of the proportion of subjects with no significant nausea during five weeks (35 days) (of treatment as above) 3. To compare the fosaprepitant regimen and the control regimen with respect to complete response in the 35 days following initiation of treatment as above. 4. To compare the fosaprepitant regimen and the control regimen in terms of the proportion of subjects with no nausea during five weeks (35 days) (of treatment as above). 5. To compare the fosaprepitant regimen and the control regimen in terms of the number of days to first emetic episode. 6. To compare quality of life using the FLIE questionnaire. 7. To compare tolerability of both regimens. ;Primary end point(s): The primary endpoint is the 'sustained no emesis rate' during five weeks of fractionated (5 days a week) radiotherapy and concomitant weekly cisplatin at a dose of = 40 mg/m2. Sustained no emesis during five weeks means that the study subject is free from vomiting episodes in the interval beginning at infusion of first dose of cisplatin untill 7 days after the infusion of the fifth dose of cisplatin.;Timepoint(s) of evaluation of this end point: After inclusion of the planned 230 | — |
Countries
Australia, Denmark, Germany, Norway
Contacts
Public ContactChristina Ruhlmann
Odense University Hospital
Outcome results
None listed