Clinical trial NCT01074697: Efficacy of Two Antiemetic Regimens in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin
Official title: A Multinational, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Tolerability of Palonosetron and Dexamethasone Plus Fosaprepitant or Placebo in Patients Receiving Radiotherapy and Weekly Cisplatin.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nausea
Vomiting
Genital Neoplasms, Female
Keywords: Randomized Controlled Trial
Serotonin Agonists
Dexamethasone
Receptors, Neurokinin-1
Radiotherapy
Cisplatin
Prevention & control
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Helsinn Healthcare SA
First posted: 2010-02-24
Enrollment: 246
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: GAND-emesis is a multinational, randomized, double-blind, placebo-controlled, parallel-group study to investigate the efficacy and tolerability of a neurokinin1 receptor antagonist (fosaprepitant dimeglumine) in combination with an antiemetic (anti-nausea-and-vomiting) control regimen (palonosetron and dexamethasone) in patients with a gynaecological cancer diagnosis, who are scheduled to receive radiotherapy and weekly chemotherapy.

The study aims at investigating if a three-drug antiemetic regimen is superior to a two-drug regimen (standard treatment) in preventing nausea and vomiting in patients receiving radiotherapy and weekly chemotherapy. A pilot study demonstrated that approximately 50% of patients will experience nausea and vomiting when offered a two-drug antiemetic regimen, and it is expected that addition of a third drug (a neurokinin1 receptor antagonist) can increase the proportion of patients with no vomiting in the course of combined chemo-radiotherapy.


Eligibility criteria: Inclusion Criteria: (abbreviated)

1. The patient has a diagnosis 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 (RT) naïve. NB: previously low voltage RT or electron RT for non-melanoma skin cancers is allowed.
5. The patient is scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2 for at least five weeks.
6. Brachy therapy is scheduled to be initiated after the third cycle of weekly cisplatin, and preferentially after the fifth week of treatment.
7. Chemotherapy with an emetic risk potential of minimal or mild (up to 30%) is allowed on days 1-4 (see ref. 14).
8. The patient has a WHO Performance Status of ≤ 2.

Exclusion Criteria: (abbreviated)

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 of fractionated radiotherapy and concomitant weekly cisplatin.
4. Brachy therapy is planned to be initiated before the third cycle of weekly cisplatin.
5. The patient has been previously treated with radiotherapy, and/or chemotherapy, with exception of treatment with low voltage RT or electron RT for non-melanoma skin cancers .
6. The patient has a WHO Performance Status of \> 2.

Primary outcomes:
measure: To compare fosaprepitant dimeglumine, palonosetron, and dexamethasone with palonosetron, dexamethasone, and placebo with respect to efficacy; the proportion of subjects with no vomiting during five weeks of radiotherapy and concomitant weekly cisplatin.
timeFrame: 35 days
Secondary outcomes:
measure: To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with complete response in the 7 days following initiation of radiotherapy and concomitant weekly cisplatin.
timeFrame: 7 days
measure: To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with no significant nausea during five weeks of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
timeFrame: 35 days
measure: To compare the fosaprepitant dimeglumine regimen and the control regimen with respect to complete response in the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
timeFrame: 35 days
measure: To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with no nausea during five weeks (35 days) of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
timeFrame: 35 days
measure: To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the number of days to first emetic episode.
timeFrame: 0-35 days
measure: To compare quality of life using the FLIE questionnaire.
timeFrame: 0-35 days
measure: To compare tolerability of both regimens.
timeFrame: 0-35 days
Other outcomes:
Locations:
city: Adelaide SA
country: Australia
facility: RAH Cancer Centre, Royal Adelaide Hospital
city: Aarhus
country: Denmark
facility: Department of Oncology
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Finsen Centret
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Department of Oncology, Odense University Hospital
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukolln
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein
city: Oslo
country: Norway
facility: The Norwegian Radium Hospital
Study officials:
affiliation: Odense University Hospital
name: Jorn Herrstedt, MD, DMSci
role: STUDY_DIRECTOR
affiliation: Odense University Hospial
name: Christina Ruhlmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Adelaide Hospital
name: Dorothy Keefe, MD, FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Vivantes Klinikum Neukölln in Berlin
name: Petra Feyer, MD, DMSci
role: PRINCIPAL_INVESTIGATOR
affiliation: Herlev Hospital
name: Thomas Broe Christensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Norwegian Radium Hospital
name: Gunnar Kristensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Finsen Centre, Copenhagen University Hospital
name: Henrik Roed, MD, DMSci
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Schleswig-Holstein
name: Felix Hilpert, MD, DMSci
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Oncology,Aarhus University Hospital, Aarhus, Denmark
name: Jacob C Lindegaard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruhlmann CH, Christensen TB, Dohn LH, Paludan M, Ronnengart E, Halekoh U, Hilpert F, Feyer P, Kristensen G, Hansen O, Keefe D, Herrstedt J. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol. 2016 Apr;17(4):509-518. doi: 10.1016/S1470-2045(15)00615-4. Epub 2016 Mar 4.