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

• Sponsor: University of South Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00429702
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 7
• Locations: 7
• Arms: 2
• Duration (Months): 25
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nausea; Vomiting; Unspecified Childhood Solid Tumor, Protocol Specific	Drug: Decadron®; Drug: Benadryl®; Drug: Ativan®; Drug: ondansetron hydrochloride	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Phase II Randomized, Double-Blinded Study of an Antiemetic Pump, Using Benadryl®, Avitan® and Decadron® (BAD), for Children Receiving Moderately or Highly Emetogenic Chemotherapy
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benadryl® Ativan® Decadron® (BAD) Pump 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®; Given IV; Other Names: dexamethasone ; Drug: Benadryl®; Given IV; Other Names: diphenhydramine hydrochloride ; Drug: Ativan®; Given IV; Other Names: lorazepam ; Drug: ondansetron hydrochloride; Given IV; Other Names: Zofran Ondisolv
Active Comparator: Control Arm Saline 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®; Given IV; Other Names: dexamethasone ; Drug: ondansetron hydrochloride; Given IV; Other Names: Zofran Ondisolv

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis During Inpatient Chemotherapy [during in-patient cycle of chemotherapy, up to 4 days]

   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.

Secondary Outcome Measures

1. Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis After Completion of the First Course of Emetogenic Chemotherapy [3 days of following completion of first chemotherapy cycle]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
2	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
3	St. Joseph's Children's Hospital of Tampa	Tampa	Florida	United States	33677-4227
4	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
5	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
6	CHRISTUS Santa Rosa Children's Hospital	San Antonio	Texas	United States	78207
7	San Jorge Children's Hospital	Santurce		Puerto Rico	00912

Sponsors and Collaborators

• University of South Florida
• National Cancer Institute (NCI)

Investigators

• Study Chair: Haydar Frangoul, MD, Vanderbilt-Ingram Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00429702
• Other Study ID Numbers: SCUSF 0503; SCUSF-0503; HLMCC-0503; U10CA081920
• First Posted: Feb 1, 2007
• Last Update Posted: Jul 25, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by University of South Florida: nausea; vomiting; emetic chemotherapy; unspecified childhood solid tumor, protocol specific
• Additional relevant MeSH terms: Nausea; Vomiting; Diphenhydramine; Promethazine; Dexamethasone; Lorazepam; Ondansetron

Study Results

Participant Flow

Recruitment Details	Recruitment took place at participating SunCoast CCOP Research Base affiliated CCOPs and MB-CCOP institutions. Potential subjects may be provided with a paper study brochure that included a brief study overview by study staff. No recruitment or dissemination of any study brochures or materials occured prior to each site obtaining IRB approval.

Arm/Group Title	Benadryl® Ativan® Decadron® (BAD) Pump	Control Arm Saline
Arm/Group Description	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. Decadron®: Given IV Benadryl®: Given IV Ativan®: Given IV ondansetron hydrochloride: Given IV	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. Decadron®: Given IV ondansetron hydrochloride: Given IV
Period Title: Overall Study
STARTED	3	4
COMPLETED	3	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Benadryl® Ativan® Decadron® (BAD) Pump	Control Arm Saline	Total
Arm/Group Description	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. Decadron®: Given IV Benadryl®: Given IV Ativan®: Given IV ondansetron hydrochloride: Given IV	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. Decadron®: Given IV ondansetron hydrochloride: Given IV	Total of all reporting groups
Overall Participants	3	4	7
Age (Count of Participants)
<=18 years	2 66.7%	4 100%	6 85.7%
Between 18 and 65 years	1 33.3%	0 0%	1 14.3%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 25%	2 28.6%
Male	2 66.7%	3 75%	5 71.4%
Region of Enrollment (participants) [Number]
United States	3 100%	4 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis During Inpatient Chemotherapy
Description	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.
Time Frame	during in-patient cycle of chemotherapy, up to 4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Benadryl® Ativan® Decadron® (BAD) Pump	Control Arm Saline
Arm/Group Description	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. Decadron®: Given IV Benadryl®: Given IV Ativan®: Given IV ondansetron hydrochloride: Given IV	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. Decadron®: Given IV ondansetron hydrochloride: Given IV
Measure Participants	3	4
Number [participants]	1 33.3%	3 75%

2. Secondary Outcome

Title	Proportion of Patients Requiring Rescue Medication for Breakthrough Nausea or Emesis After Completion of the First Course of Emetogenic Chemotherapy
Description	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.
Time Frame	3 days of following completion of first chemotherapy cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Benadryl® Ativan® Decadron® (BAD) Pump	Control Arm Saline
Arm/Group Description	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. Decadron®: Given IV Benadryl®: Given IV Ativan®: Given IV ondansetron hydrochloride: Given IV	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. Decadron®: Given IV ondansetron hydrochloride: Given IV
Measure Participants	3	4
Number [participants]	3 100%	4 100%

Adverse Events

Time Frame	Adverse events (AEs) were assessed daily beginning with the first cycle of chemotherapy and administration of study agent/placebo until 3 days following completion of chemotherapy cycle.
Adverse Event Reporting Description	AEs were assessed by study staff during in-patient chemotherapy, at discharge and 3 days following completion of chemotherapy with patient and patient's primary caregiver. AEs were also assessed using the Adapted Rhodes Index of Nausea, Vomiting and Retching Measured by Children and Parents that were completed twice daily.
Arm/Group Title	Benadryl® Ativan® Decadron® (BAD) Pump		Control Arm Saline
Arm/Group Description	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. Decadron®: Given IV Benadryl®: Given IV Ativan®: Given IV ondansetron hydrochloride: Given IV		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. Decadron®: Given IV ondansetron hydrochloride: Given IV
All Cause Mortality
	Benadryl® Ativan® Decadron® (BAD) Pump		Control Arm Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Benadryl® Ativan® Decadron® (BAD) Pump		Control Arm Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Benadryl® Ativan® Decadron® (BAD) Pump		Control Arm Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/4 (25%)
Surgical and medical procedures
Pain associated with biopsy	0/3 (0%)	0	1/4 (25%)	1

Limitations/Caveats

The study was closed prior to completing enrollment based on the recommendation by the SunCoast CCOP Research Base Data Safety Monitoring Board for a lack of feasibility and poor enrollment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.