This is a multicentre, single-arm, phase II study to investigate the safety and antiemetic efficacy of Akynzeo (a fixed dose combination of palonosetron and netupitant) plus dexamethasone in patients receiving concomitant chemo-radiotherapy with weekly cisplatin for at least five weeks.
Akynzeo contains a combination of the neurokinin-1 receptor antagonist netupitant and the serotonin receptor antagonist palonosetron. Akynzeo is approved as antiemetic prophylaxis in patients receiving high emetogenic chemotherapy e.g. high dose cisplatin administered every three weeks. From a previous clinical trial (GAND-emesis trial) we know that patients receiving radiotherapy and concomitant weekly cisplatin 40 mg/m2 are better protected against nausea and vomiting when a triplet antiemetic prophylaxis (neurokinin-1 receptor antagonist, serotonin receptor antagonist, and corticosteroid) is applied. In the Akynzeo phase III clinical trials, Akynzeo was administered every three weeks. The neurokinin-1 receptor antagonist, netupitant, has a long plasma half-life (approx. 90 hours), and theoretically the drug could accumulate when administered on a weekly basis. The DANGER-emesis trial is designed to collect safety and efficacy data in patients receiving Akynzeo weekly as antiemetic prophylaxis in combination with dexamethasone in patients treated for cervical cancer with radiotherapy and concomitant weekly cisplatin 40 mg/m2.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
80
Weekly administration of akynzeo for five weeks.
Weekly administration of dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for five weeks.
Department of Oncology, Odense University Hospital
Odense, Denmark
RECRUITINGSafety of weekly administration of Akynzeo measured by incidence of treatment-emergent adverse events
Measurement of incidence of treatment-emergent adverse events.
Time frame: Five weeks.
Efficacy of weekly administration of Akynzeo measured by incidence of nausea and vomiting and use of rescue antiemetics
Measurement of incidence of nausea and vomiting and use of rescue antiemetics.
Time frame: Five weeks.
Complete response in terms of the proportion of subjects with complete response
To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with complete response (defined as no vomits, no dry retches and no need for rescue medication) in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
Time frame: Five days and five weeks.
No significant nausea in terms of the proportion of subjects with no significant nausea
To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with no significant nausea (none or mild nausea) in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
Time frame: Five days and five weeks.
No nausea in terms of the proportion of subjects with no nausea
To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with no nausea in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
Time frame: Five days and five weeks.
Time to first emetic episode
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To investigate Akynzeo and dexamethasone in terms of time to first emetic episode.
Time frame: Five weeks.