Treatment Algorithm for Nausea and Vomiting in the Palliative Phase

Sponsor

Radboud University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03017391

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

Brief Summary

Nausea and vomiting are frequently occurring problems in the palliative phase of patients with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.

Condition or Disease	Intervention/Treatment	Phase
Nausea Vomiting Cancer	Drug: metoclopramide Drug: granisetron Drug: Dexamethasone Drug: Granisetron 2Mg Tablet	Phase 4

Detailed Description

Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin antagonists, the combination of both and dexamethasone as rescue medication in case of failure. There is no data that depicts which strategy is the best. This study will be conducted to unravel which treatment algorithm is most successful: 1 to start with metoclopramide, to add a serotonin antagonist (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient can swallow) in case of failure and to add dexamethasone as rescue medication versus 2 an algorithm to start with a serotonin antagonist (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient can swallow), to add metoclopramide in case of failure and to add dexamethasone as rescue medication. Granisetron plaster is a new formulation of a well known serotonin antagonist and might be useful especially within the patient group in the palliative phase.

The questions are:

Is it feasible to compare treatment algorithms for symptomatic treatment of nausea and vomiting in palliative cancer patients? And is a stepwise symptomatic treatment algorithm to manage nausea and vomiting using metoclopramide or granisetron transdermal patch as a start medication effective in palliative patients in at least one of both treatment arms? Patients will be asked to complete the QLQC30 and ESAS on different moments during the study. Besides, they will be asked to complete a diary for nausea severity (NRS scale 0-10) and for the frequency of vomiting and retching twice daily.

Success of a treatment algorithm is defined as nausea is < 3 on NRS or a decrease of >2 on NRS for nausea combined with an absence of vomiting or retching in the last 3 days. Incomplete success is defined as nausea of 3 on NRS during one occasion of the last 3 days before the end of study but less than 4, no more than one retching a day during that period and absence of vomiting. Complete failure is defined as nausea of 4 or more on an NRS during the last 3 days or more than one retching daily or any vomiting or in case the patient has stopped all medication due to side effects.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Feasibility Study to Compare 2 Strategies of Treatment Algorithm for Treating Nausea and or Vomiting in the Palliative Phase of Cancer Care

Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: algorithm 1 first metoclopramide metoclopramide 10 mg tablets 3x daily orally and in those patients that cannot swallow tablets the medication will be substituted by suppositories 10 mg 3x daily rectally. In case of failure, granisetron patch 3.1mg/24 hours will be added to the treatment and a loading dose of 2 mg granisetron oral if the patient can swallow. In case of toxicity metoclopramide will be stopped. In case of failure of the combination (second step) or toxicity, an oral dose of dexamethasone 8 mg will be added daily.	Drug: metoclopramide metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity Drug: granisetron granisetron patch 3.1mg/24 hours, use until toxicity Other Names: Sancuso Drug: Dexamethasone dexamethasone 8 mg, last step in both algorithms Drug: Granisetron 2Mg Tablet granisetron 2 mg loading dose
Active Comparator: algorithm 2 first granisetron granisetron patch 3.1 mg/24 hours will be offered to the patient, and a loading dose of 2 mg granisetron oral if the patient can swallow In case of failure, metoclopramide 10 mg tablets 3x daily orally will be added and in those patients that cannot swallow tablets the oral medication will be substituted with rectal suppositories 10 mg. The granisetron patch will only be withdrawn from patients that suffer from clinically relevant toxicity. Metoclopramide will then be administered. In the case of secondary failure or toxicity, dexamethasone 8 mg orally daily will be added.	Drug: metoclopramide metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity Drug: granisetron granisetron patch 3.1mg/24 hours, use until toxicity Other Names: Sancuso Drug: Dexamethasone dexamethasone 8 mg, last step in both algorithms Drug: Granisetron 2Mg Tablet granisetron 2 mg loading dose

Arm

Intervention/Treatment

Active Comparator: algorithm 1 first metoclopramide

metoclopramide 10 mg tablets 3x daily orally and in those patients that cannot swallow tablets the medication will be substituted by suppositories 10 mg 3x daily rectally. In case of failure, granisetron patch 3.1mg/24 hours will be added to the treatment and a loading dose of 2 mg granisetron oral if the patient can swallow. In case of toxicity metoclopramide will be stopped. In case of failure of the combination (second step) or toxicity, an oral dose of dexamethasone 8 mg will be added daily.

Drug: metoclopramide

metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity

Drug: granisetron

granisetron patch 3.1mg/24 hours, use until toxicity

Other Names:

Sancuso

Drug: Dexamethasone

dexamethasone 8 mg, last step in both algorithms

Drug: Granisetron 2Mg Tablet

granisetron 2 mg loading dose

Active Comparator: algorithm 2 first granisetron

granisetron patch 3.1 mg/24 hours will be offered to the patient, and a loading dose of 2 mg granisetron oral if the patient can swallow In case of failure, metoclopramide 10 mg tablets 3x daily orally will be added and in those patients that cannot swallow tablets the oral medication will be substituted with rectal suppositories 10 mg. The granisetron patch will only be withdrawn from patients that suffer from clinically relevant toxicity. Metoclopramide will then be administered. In the case of secondary failure or toxicity, dexamethasone 8 mg orally daily will be added.

Drug: metoclopramide

metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity

Drug: granisetron

granisetron patch 3.1mg/24 hours, use until toxicity

Other Names:

Sancuso

Drug: Dexamethasone

dexamethasone 8 mg, last step in both algorithms

Drug: Granisetron 2Mg Tablet

granisetron 2 mg loading dose

Outcome Measures

Primary Outcome Measures

NRS nausea [15 days]
response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days

Secondary Outcome Measures

days from T0 to control [two weeks]
The time from T0 until the moment that nausea and vomiting/retching is in control

Other Outcome Measures

feasibility [6 months]
number of included patients a 6 months period
comparison of starting metoclopramide to starting with granisetron [6 months]
response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days
quality of life [15 days]
QLQC30 scale
adverse events [14/15 days]
diary adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients 18 years or older in the palliative phase and
who suffer from nausea or vomiting with a rating on a numeric rating scale (NRS) of more than 2 and
have a wish to be treated and
where no treatable cause is assignable