Efficacy of Two Antiemetic Regimens in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Nausea, Vomiting, Genital Neoplasms, Female

Intervention / Treatment
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* Drug: Fosaprepitant dimeglumine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (abbreviated) The patient has a diagnosis cervical cancer. The patient understands the nature and purpose of this study and the study procedures and has signed informed consent. The patient is aged > 18 years. 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. The patient is scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2 for at least five weeks. Brachy therapy is scheduled to be initiated after the third cycle of weekly cisplatin, and preferentially after the fifth week of treatment. Chemotherapy with an emetic risk potential of minimal or mild (up to 30%) is allowed on days 1-4 (see ref. 14). The patient has a WHO Performance Status of ≤ 2. Exclusion Criteria: (abbreviated) The patient has a current malignant diagnosis other than cervical cancer, with exception of non-melanoma skin cancers. The patient is aged < 18 years. The patient is scheduled to receive less than five weeks of fractionated radiotherapy and concomitant weekly cisplatin. Brachy therapy is planned to be initiated before the third cycle of weekly cisplatin. 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 . The patient has a WHO Performance Status of > 2.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fosaprepitant dimeglumine<br> | Drug: Fosaprepitant dimeglumine<br>* Addition of fosaprepitant dimeglumine 150 mg IV single dose weekly (before chemotherapy) to dexamethasone and palonosetron.<br>* Other names: Dexamethasone;|
| Placebo Comparator: Saline water<br> | Drug: Placebo<br>* Saline water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 7 days | 
| 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. |  | 35 days | 
| 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. |  | 35 days | 
| 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. |  | 35 days | 
| To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the number of days to first emetic episode. |  | 0-35 days | 
| To compare quality of life using the FLIE questionnaire. |  | 0-35 days | 
| To compare tolerability of both regimens. |  | 0-35 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Controlled Trial, Serotonin Agonists, Dexamethasone, Receptors, Neurokinin-1, Radiotherapy, Cisplatin, Prevention & control