Diphenhydramine, Lorazepam, and Dexamethasone in Treating Nausea and Vomiting Caused By Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Diphenhydramine, lorazepam, and dexamethasone may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. It is not yet known whether diphenhydramine, lorazepam, and dexamethasone are more effective than standard therapy in treating nausea and vomiting caused by chemotherapy. PURPOSE: This randomized phase II trial is studying diphenhydramine, lorazepam, and dexamethasone to see how well they work compared with standard therapy in treating nausea and vomiting caused by chemotherapy in young patients with newly diagnosed cancer.

Detailed Description
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OBJECTIVES: Primary Compare the degree of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients with newly diagnosed cancer treated with diphenhydramine hydrochloride, lorazepam, and dexamethasone vs standard antiemetic therapy during the first course of emetogenic chemotherapy. Secondary Compare the degree of CINV during the first 3 days after completion of the first course of emetogenic chemotherapy in patients treated with these antiemetic regimens. OUTLINE: This is a randomized, prospective, double-blind, multicenter study. Patients are stratified according to the emetogenic potential of their chemotherapy regimen (high vs moderate). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive ondansetron hydrochloride IV twice daily and saline IV twice daily beginning 30-60 minutes prior to the start of chemotherapy. Patients also receive diphenhydramine hydrochloride, lorazepam, and dexamethasone by continuous infusion pump. Arm II: Patients receive ondansetron hydrochloride IV twice daily and dexamethasone IV twice daily beginning 30-60 minutes prior to the start of chemotherapy. Patients also receive saline by continuous infusion pump. In both arms, treatment continues during the first course of chemotherapy. Patients may also receive rescue antiemetic medication to control breakthrough nausea or emesis. Patients and their parents complete the Adapted Rhodes Index of Nausea, Vomiting, and Retching- Measured by Child/Parent questionnaire once before beginning chemotherapy, twice daily during chemotherapy, and for 3 days after completion of chemotherapy. PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.

Official Title
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Phase II Randomized, Double-Blinded Study of an Antiemetic Pump, Using Benadryl®, Avitan® and Decadron® (BAD), for Children Receiving Moderately or Highly Emetogenic Chemotherapy

Conditions
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Nausea, Vomiting, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: Decadron®
* Drug: Benadryl®
* Drug: Ativan®
* Drug: ondansetron hydrochloride


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: ≥ 8 years of age and < 19 years of age at the time of registration Newly diagnosed with cancer Chemotherapy naive Scheduled to receive moderately or highly emetogenic chemotherapy (non-steroid containing regimen) as an in-patient. (Refer to Appendix IV. In multiple agent regimens, select the agent with the highest emetic potential.) Scheduled for placement of IV accesses device(s) for treatment purposes (allowing a dedicated line for continuous infusion of study agent) Not pregnant or lactating EXCLUSION CRITERIA: Prior chemotherapy Central Nervous System disease Stem cell transplant while on-study Out-patient chemotherapy Steroids are included in their chemotherapy regimen Contraindication to the use of dexamethasone (e.g. diabetes) Hepatic and/or renal failure Allergic to any of the study medications Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benadryl® Ativan® Decadron® (BAD) Pump<br>Patients receive ondansetron hydrochloride IV twice daily and saline IV twice daily beginning 30-60 minutes prior to the start of chemotherapy. Patients also receive diphenhydramine hydrochloride, lorazepam, and dexamethasone by continuous infusion pump. | Drug: Decadron®<br>* Given IV<br>* Other names: dexamethasone;Drug: Benadryl®<br>* Given IV<br>* Other names: diphenhydramine hydrochloride;Drug: Ativan®<br>* Given IV<br>* Other names: lorazepam;Drug: ondansetron hydrochloride<br>* Given IV<br>* Other names: Ondisolv;|
| Active Comparator: Control Arm Saline<br>Patients receive ondansetron hydrochloride IV twice daily and dexamethasone IV twice daily beginning 30-60 minutes prior to the start of chemotherapy. Patients also receive saline by continuous infusion pump. | Drug: Decadron®<br>* Given IV<br>* Other names: dexamethasone;Drug: ondansetron hydrochloride<br>* Given IV<br>* Other names: Ondisolv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis During Inpatient Chemotherapy | Rescue medication is any medication administered by the treating team to control breakthrough nausea or emesis. Rescue medications were used to treat any patient who has enough symptoms requiring additional therapy. All patients were instructed to first use the push button on the pump. On-demand administration of study agent via the patient-controlled infusion pump will not be considered rescue therapy - it is part of the antiemetic treatment regimen. If on-demand administration is not successful in controlling the patient's symptoms, then as-needed rescue medications are to be administered. The treating staff will administer additional (as needed) doses of intravenous antiemetics, depending on the institutional preference. | during in-patient cycle of chemotherapy, up to 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis After Completion of the First Course of Emetogenic Chemotherapy | CINV will be determined based on the number of rescue medications used during the 3 days following completion of chemotherapy cycle. Rescue medication is any medication administered by the treating team to control breakthrough nausea or emesis. Rescue medications were used to treat any patient who has enough symptoms requiring additional therapy. All patients were instructed to first use the push button on the pump. On-demand administration of study agent via the patient-controlled infusion pump will not be considered rescue therapy - it is part of the antiemetic treatment regimen. If on-demand administration is not successful in controlling the patient's symptoms, then as-needed rescue medications are to be administered. The treating staff will administer additional (as needed) doses of intravenous antiemetics, depending on the institutional preference. | 3 days of following completion of first chemotherapy cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, vomiting, emetic chemotherapy, unspecified childhood solid tumor, protocol specific