E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients naive to chemotherapy diagnosed with a solid malignant tumor scheduled to receive a moderately emetogenic chemotherapy regimen. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054133 |
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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 |
The primary objective of this study is to demonstrate the superiority of triple therapy, casopitant, ZOFRAN and dexamethasone over dual therapy, ZOFRAN and dexamethasone in the control of emesis over the first 120 hours following the initiation of the first cycle of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy MEC regimen. |
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E.2.2 | Secondary objectives of the trial |
Determine whether the addition of casopitant provides incremental improvement in the prevention of emesis in the acute 0-24 hrs. and delayed 24-120 hrs. phase following the first cycle of MEC. Determine whether the addition of casopitant provides incremental improvement in the prevention of emesis in the acute 0-24 hrs. , delayed 24-120 hrs. and overall 0-120 hrs. phase following subsequent cycles of MEC. Determine whether the addition of casopitant provides incremental improvement in the control of nausea over the first 120 hours and in the acute and delayed phase following each cycle of MEC. Quantify the impact of the antiemetic regimens on daily life activities, as assessed by a Functional Living Index-Emesis FLIE questionnaire following the first cycle of MEC. Assess subject satisfaction with the prophylactic antiemetic regimen, and the willingness of subjects to use the same regimen during future chemotherapy treatments. Determine the safety a |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Subject understands the nature and purpose of this study and the study procedures and has signed an informed consent form for this study to indicate this understanding. 2.At least 18 years of age. 3.Is scheduled to receive their first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy regimen for the treatment of a solid malignant tumor as outlined in Section 8.1.1. 4.Has a Karnofsky Performance Status of at least 70 5.Hematologic and metabolic status must be adequate for receiving a moderately emetogenic regimen and meet the following criteria Total Neutrophils 8805; 1500/mm3 Standard units 8805;1.5 x 109/L Platelets 8805; 100,000/mm3 Standard units 8805;100.0 x 109/L Bilirubin 8804; 1.5 x ULN Liver enzymes must be below the following limits -Without known liver metastases Aspartate aminotransferase AST and/or alanine aminotransferase ALT 8804; 2.5 x upper limit of normal. -With known liver metastases AST and/or ALT 8804; 5.0 x upper limit of normal. 6.Is willing and able to complete daily components of the subject diary for each study cycle. 7.Women of childbearing potential; must commit to consistent and correct use of an acceptable method of birth control; GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of a physician, are as follows a.Non-childbearing potential i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses b.child-bearing potential must have a negative serum pregnancy test result or negative urine dipstick pregnancy test within 24 hours prior to the first dose of investigational product of Cycle 1, Day 1 and agrees to one of the following male partner who is sterile prior to the female subject s entry into the study and is the sole sexual partner for that female subject oral contraceptives e.g., oral, injectable, or implantable with double-barrier method of contraception consisting of spermicide with either condom or diaphragm for a period after the trial to account for potential drug interaction minimum of six weeks double-barrier method of contraception consisting of spermicide with either condom or diaphragm intra-uterine device IUD with a documented failure rate of less than 1 per year complete abstinence from intercourse for two weeks before exposure to the investigational product throughout the clinical trial, and for a period after the trial to account for elimination of the drug minimum of three days , if subjects indicate they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active. |
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E.4 | Principal exclusion criteria |
1.Has previously received cytotoxic chemotherapy. A history of previous biological or hormonal therapy will be permitted. 2.Is a female subject who is pregnant or lactating. 3.Has received radiation therapy to the brain, abdomen or pelvis in the ten days prior to the first dose of study medication or casopitant investigational product and/or will receive radiation therapy to the brain, abdomen or the pelvis in the six days following the first dose of study medication ZOFRAN and dexamethasone or casopitant investigational product. 4.Is scheduled to receive taxane therapy during cycle 1. Note that subjects will be permitted to receive taxane therapy in conjunction with one of the allowed MEC regimens during subsequent cycles. 5.Has experienced emesis i.e., vomiting and/or retching or clinically significant nausea in the 24 hours preceding the first dose of study medication or casopitant investigational product. 6.Has a known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been medically stable for at least 1 week prior to receiving the first dose of study medication or casopitant investigational product. 7.Has history of documented peptic ulcer disease via endoscopy or x-ray , 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 or pose an unwarranted risk to the subject. 8.Has a known hypersensitivity or contraindication to ZOFRAN, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant. 9.Has previously received an NK-1 receptor antagonist. 10.Received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug other than casopitant during the study period. 11.Has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medication or casopitant investigational product. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose and has not experienced emesis or nausea from the narcotics. 12.Has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drug. This includes, but is not limited to 5-HT3 receptor antagonists e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron . Palonestron is not permitted within 7 days prior to administration of investigational product. benzamide / benzamide derivatives e.g., metoclopramide, alizapride 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 the first dose of casopitant investigational product; however, lorazepam is prohibited phenothiazines e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine butyrophenone e.g., haloperidol, droperidol corticosteroids e.g., dexamethasone, methylprednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders, and prophylactic treatment for taxane therapy during subsequent cycles anticholinergics e.g., scopolamine antihistamines e.g., cyclizine, hydroxyzine, diphenhydramine , except for prophylactic use for taxane therapy during cycle 2-4 see Section 8.1.1 domperidone cannabinoids mirtazpine olanzapine 13.Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of casopitant investigational product see Section 8.2.2 Inhibitors of CYP3A4 and CYP3A5 14.Has taken/received inducers of CYP3A4 and CY |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportion of subjects who achieve a complete response defined as no vomiting/retching, and no rescue therapy over the first 120 hours following the initiation of their first cycle of an anthracycline and cyclophosphamide containing MEC regimen. |
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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 | 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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | Yes |
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
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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 | 8 |
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 | 8 |