Chemotherapy-Induced Nausea and Vomiting (CINV) - Highly Emetogenic Chemotherapy (HEC)
Conditions
Sponsors
GlaxoSmithKline Group of Companies
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male, or female at least 18 years of age. 2. Diagnosed with a malignant solid tumour and is scheduled to receive the first course of chemotherapy with cisplatin as a single intravenous dose of > 70 mg/m2 on study Day 1, given over a duration of between 1 and 4 hours (as per local institutional standards), either alone or in combination with other chemotherapeutic agents. Additional chemotherapeutic agents of low to high emetogenic potential (e.g. cyclophosphamide, doxorubicin, ifosfamide), must be administered after the initiation of cisplatin and be completed within 6 hours from the time that cisplatin was initiated. Chemotherapeutic agents of low emetogenic potential (e.g., gemcitabine), may be administered at the time of or after the initiation of cisplatin administration, as per usual institutional practices. Taxanes (e.g., paclitaxel, docetaxel) may be administered on study Day 1 only. 3. A Karnofsky Performance Scale score of at least 70 4. Adequate haematologic and metabolic status for receiving cisplatin chemotherapy: - WBC > 3000/mm3. - Platelets > 100,000/mm3. - Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has previously received cytotoxic chemotherapy. 2. Is scheduled to receive greater than 1 day of cisplatin treatment during a single cycle of therapy. 3. Is scheduled to receive adjuvant chemotherapy with cyclophosphamide-containing regimens. 4. Pregnant or lactating. 5. An unwillingness of the male subject to use a condom with spermicide in addition to having their female partner use another form of contraception. 6. Has received radiation therapy to the abdomen or the pelvis in the 7 days prior to receiving the first dose of study medication or will receive radiation therapy to the abdomen or the pelvis in the 6 days following the first dose of study medication. 7. Emesis (i.e., vomiting and/or retching) experienced in the 24 hours prior to receiving the first dose of study medication. 8. Clinically significant nausea in the 24 hours prior to receiving the first dose of study medication. 9. A known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been stable for at least 1 week prior to receiving the first dose of study medication. 10. An etiology for emesis and nausea including, but not limited to, gastrointestinal obstruction, increased intracranial pressure, hypercalcaemia, active peptic ulcer. 11. Any known history of peptic ulcer disease or irritable bowel disease. 12. An active systemic infection or any uncontrolled disease (other than malignancy) which, in the opinion of the Investigator, may confound the results of the study. Subjects with a previous, but not current, history of alcoholism may be permitted provided that, in the Investigator's opinion, the subject's disease state will not confound the results of the study. 13. Initiated systemic corticosteroid therapy at any dose within 72 hours prior to receiving the first dose of study medication except where indicated as prophylactic medication for taxane therapy(e.g., paclitaxel or docetaxel). 14. Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of cisplatin therapy. 15. A known hypersensitivity or contraindication to ondansetron hydrochloride or ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of GW679769. 16. Has previously received an NK-1 receptor antagonist. 17. Has received any investigational drug within the 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication and/or is scheduled to receive any investigational drug during the study. 18. Has received moderately and/or highly emetogenic medication within the 48 hours prior to the first dose of study medication. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose of such medication for at least 7 days and has experienced neither emesis nor nausea from the narcotics. 19. Has taken/received palonosetron within 7 days prior to the initial dose of study medication/investigational product. 20. 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). - Benzamide / benzamide derivatives (e.g., metoclopramide, alizapride). - Benzodiazepines (except if the subject is receiving such medication for sleep and has been on a stable dose for at least 7 days prior to the first dose of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the optimal antiemetic dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of emesis during the first 120 hours following initiation of the first cycle of highly emetogenic cisplatin-based chemotherapy.;Secondary Objective: - Determine the optimal dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of nausea. -To determine the safety and tolerability profile of oral GW679769 at various dose levels when administered in combination with ondansetron hydrochloride and dexamethasone in subjects receiving their first cycle of highly emetogenic cisplatin-based chemotherapy. - To evaluate population pharmacokinetics and pharmacodynamics (PK/PD) of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone. - To compare the efficacy of GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone to that of aprepitant administered in combination with ondansetron hydrochloride and dexamethasone. - To compare the antiemetic efficacy and tolerability of single and repeat (3 days) dosing with GW679769 in combination with ondansetron hydrochloride and dexamethasone. ;Primary end point(s): The primary endpoint of this clinical trial is the proportion of subjects who achieve a complete response (defined as no vomiting, no retching, no rescue therapy, and no premature discontinuation from the study) for each treatment arm during the 120 hour evaluation period following initiation of highly emetogenic cisplatin-based chemotherapy. | — |
Countries
Czech Republic, Hungary, Italy
Outcome results
None listed